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Publisher: John Wiley and Sons   (Total: 1589 journals)

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Showing 1 - 200 of 1589 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 48, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 53, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 168, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 6, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 37, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 5)
Addiction     Hybrid Journal   (Followers: 36, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 14, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 295, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 11)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 152, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 93, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 35, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 13, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 290, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 16, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 18, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 138, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 20)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 179)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 229, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 48, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 91, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 50, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 209, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 50, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 32, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 29, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 26, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 13, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 274, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 54, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 326, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (Followers: 1, SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 3, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 47, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 6, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 15, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 419, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 23, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 5, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 152, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 7, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 247, SJR: 2.083, h-index: 125)

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Journal Cover American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
  [SJR: 1.771]   [H-I: 107]   [4 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Online) 1552-485X
   Published by John Wiley and Sons Homepage  [1589 journals]
  • Longitudinal interplays of estrogen receptor alpha gene rs9340799 with
           social‐environmental factors on post‐traumatic stress disorder in
           Chinese Han adolescents after Wenchuan earthquake
    • Authors: Yue Feng; Mi Su, Yan Jun Si, Qi Wei Guo, Jia Lin, Ting Cao, Xin Zhang, Mei Fan, Ding Zhi Fang
      Abstract: Indirect evidences suggested associations of estrogen receptor alpha (ESR1) with post‐traumatic stress disorder (PTSD). However, the relationship between rs9340799 on ESR1 gene and PTSD has not been reported yet. The present study was to explore the longitudinal changes of prevalence and severity of PTSD in adolescents with different genotypes of rs9340799 after the 2008 Wenchuan earthquake. Social‐environmental factors were collected by questionnaires in 465 high school students. Variants of rs9340799 were determined by polymerase chain reaction‐restriction fragment length polymorphism analyses and verified by DNA sequencing. PTSD symptoms were assessed by PTSD Checklist‐Civilian Version (PCL‐C) at 6, 12, and 18 months after the earthquake. The female AA homozygotes had a trend of higher prevalence of PTSD and significantly higher PCL‐C scores than the female G allele carriers at 6 months after the earthquake. The female students had higher prevalence of PTSD and higher PCL‐C scores than the male subjects at 6 months in the AA homozygotes, but not in the G allele carriers. Consecutive decreases in PCL‐C scores were observed only in the female AA homozygotes. Only in the female, the AA genotype was the risk factor and predictor of PCL‐C scores at 6 months. Potential factors of PTSD prevalence and predictors of PCL‐C scores were different between the AA homozygotes and G allele carriers at different time during the follow‐up. These results suggest gene‐environment interactions may occur among rs9340799 and social‐environmental factors, and influence the development and natural rehabilitation of PTSD in the course after stressed by the earthquake.
      PubDate: 2017-12-18T04:23:59.763831-05:
      DOI: 10.1002/ajmg.b.32615
       
  • A comprehensive review of genetic and epigenetic mechanisms that regulate
           BDNF expression and function with relevance to major depressive disorder
    • Authors: Benjamin Hing; Leela Sathyaputri, James B. Potash
      Abstract: Major depressive disorder (MDD) is a mood disorder that affects behavior and impairs cognition. A gene potentially important to this disorder is the brain derived neurotrophic factor (BDNF) as it is involved in processes controlling neuroplasticity. Various mechanisms exist to regulate BDNF's expression level, subcellular localization, and sorting to appropriate secretory pathways. Alterations to these processes by genetic factors and negative stressors can dysregulate its expression, with possible implications for MDD. Here, we review the mechanisms governing the regulation of BDNF expression, and discuss how disease‐associated single nucleotide polymorphisms (SNPs) can alter these mechanisms, and influence MDD. As negative stressors increase the likelihood of MDD, we will also discuss the impact of these stressors on BDNF expression, the cellular effect of such a change, and its impact on behavior in animal models of stress. We will also describe epigenetic processes that mediate this change in BDNF expression. Similarities in BDNF expression between animal models of stress and those in MDD will be highlighted. We will also contrast epigenetic patterns at the BDNF locus between animal models of stress, and MDD patients, and address limitations to current clinical studies. Future work should focus on validating current genetic and epigenetic findings in tightly controlled clinical studies. Regions outside of BDNF promoters should also be explored, as should other epigenetic marks, to improve identification of biomarkers for MDD.
      PubDate: 2017-12-15T08:20:55.024631-05:
      DOI: 10.1002/ajmg.b.32616
       
  • Emotional and behavioral problems in children and adolescents with
           neurofibromatosis type 1
    • Authors: André B. Rietman; Thijs van der Vaart, Ellen Plasschaert, Bethany A. Nicholson, Rianne Oostenbrink, Lianne C. Krab, Mie-Jef Descheemaeker, Marie-Claire Y.de Wit, Henriëtte A. Moll, Eric Legius, Pieter F.A.de Nijs
      Abstract: To assess emotional and behavioral problems in children and adolescents with neurofibromatosis type 1,parents of 183 individuals aged 10.8 ± 3.1 years (range 6‐17) completed the Child Behavior Checklist (CBCL). Also, 173 teachers completed the Teacher's Report Form (TRF), and 88 adolescents (children from 11 to 17 years) completed the Youth Self‐Report (YSR). According to parental ratings, 32% scored in the clinical range (above the 90th percentile). This percentage was much lower when rated by teachers or adolescents themselves. Scores from all informants on scales for Somatic complaints, Social problems, and Attention problems were significantly different from normative scores. Attentional problems were associated with lower verbal IQ, male gender, younger age, and ADHD‐symptoms. Disease‐related factors did not predict behavioral problems scores. Substantial emotional and behavioral problems were reported by parents, teachers, and to a lesser extent by adolescents with NF1 themselves. Possibly, a positive illusory bias affects the observation of behavioral problems by adolescents with NF1.
      PubDate: 2017-12-15T08:20:44.373722-05:
      DOI: 10.1002/ajmg.b.32612
       
  • Familial transmission of externalizing syndromes in extended Swedish
           families
    • Authors: Kenneth S. Kendler; Henrik Ohlsson, Jan Sundquist, Kristina Sundquist
      Abstract: Risk for criminal behavior (CB), alcohol use disorder (AUD), and drug abuse (DA) are known to be familial. We know less about their transmission across three generations. We examined 844,109 probands born in Sweden 1980–1990, their parents, aunts/uncles, and grandparents for registration in population‐based registers for CB, AUD, and DA. Mean tetrachoric relative‐proband correlations (95% CIs) were highest for DA (+0.24, 0.24–0.25), followed by CB (+0.23,0.22–0.23) and AUD (+0.17, 0.16–0.17). AUD and CB were relatively stably transmitted across generations, while DA resemblance among relatives was stronger in the younger generations. For all three syndromes, male‐male transmission was modestly stronger than female–female. Cross‐sex transmission was significantly weaker than same‐sex transmission for DA and CB but not AUD. Risk to probands with only an affected grandparent or aunt/uncle were increased 50–60% for CB and AUD, and 70–100% for DA. Parallel figures for affected parents only and parents + grandparent or aunt/uncle were 2–3‐fold and 4–5‐fold for CB and AUD, and 4–5‐fold and 6–7‐fold for DA. CB, AUD, and DA are all substantially familial in the Swedish population with the transmission across three generations stable for CB and AUD but not DA. Modest quantitative sex effects are seen in the familial transmission of CB, AUD, and DA, and qualitative sex effects for CB and DA. Risk prediction in offspring is orderly with affection status in grandparental and avuncular relationships adding appreciably to that from the parental generation.
      PubDate: 2017-12-15T08:20:35.295873-05:
      DOI: 10.1002/ajmg.b.32611
       
  • Cover Image, Volume 177B, Number 1, January 2018
    • Authors: Sali M. K. Farhan; Tania F. Gendron, Leonard Petrucelli, Robert A. Hegele, Michael J. Strong
      Abstract: The cover image, by Sali M. K. Farhan et al., is based on the Research Article OPTN p.Met468Arg and ATXN2 intermediate length polyQ extension in families with C9orf72 mediated amyotrophic lateral sclerosis and frontotemporal dementia,
      DOI : 10.1002/ajmg.b.32606.
      PubDate: 2017-12-12T09:58:44.546103-05:
       
  • Polygenic risk scores distinguish patients from non‐affected adult
           relatives and from normal controls in schizophrenia and bipolar disorder
           multi‐affected kindreds
    • Authors: Sébastien Boies; Chantal Mérette, Thomas Paccalet, Michel Maziade, Alexandre Bureau
      Abstract: Recent studies have used results on SNP association with schizophrenia (SZ) and bipolar disorder (BD) to create polygenic risk scores (PRS) discriminating non‐familial unrelated patients from controls. Little is known about the role of PRS in densely affected multigenerational families. We tested PRS differences between affected SZ and BD family members from their non‐affected adult relatives (NAARs) in Eastern Quebec Kindreds and from controls. We examined 1227 subjects: from 17 SZ and BD kindreds, we studied 153 patients (57 SZ, 13 schizoaffective, and 83 BD) and 180 NAARs, and 894 unrelated controls from the Eastern Quebec population. PRS were derived from published case‐control association studies of SZ and BD. We also constructed a combined SZ and BD PRS by using SNPs from both SZ and BD PRS. SZ patients had higher SZ PRS than controls (p = 0.0039, R2 = 0.027) and BD patients had higher BD PRS than controls (p = 0.013, R2 = 0.027). Differences between affected subjects and NAARs and controls were significant with both SZ and BD PRS. Moreover, a combined SZ‐BD PRS was also significantly associated with SZ and BD when compared to NAARs (p = 0.0019, R2 = 0.010) and controls (p = 0.0025, R2 = 0.028), revealing a SZ‐BD commonality effect in PRS at the diagnosis level. The SZ and the BD PRS, however, showed a degree of specificity regarding thought disorder symptoms. Overall, our report would confirm the usefulness of PRS in capturing the contribution of common genetic variants to the risk of SZ and BD in densely affected families.
      PubDate: 2017-11-28T10:45:35.788447-05:
      DOI: 10.1002/ajmg.b.32614
       
  • Mutation spectra and founder effect of TMC1 in patients with
           non‐syndromic deafness in Xiamen area, China
    • Authors: Yi Jiang; Song Gao, Lihua Wu, Xiaohua Jin, Tao Deng, Ligang Wang, Shasha Huang, Xue Gao, Juan Chen, Dongyi Han, Huafang Gao, Pu Dai
      Abstract: To analyze the spectrum and founder effect of TMC1 mutations in patients with non‐syndromic deafness in the Xiamen area. Sporadic pedigrees were detected by targeted next‐generation sequencing, and 110 unrelated patients from Xiamen Special Education School were analyzed through Sanger sequencing for the TMC1 gene. In total, 53 SNPs were designed to analyze the haplotypes of the TMC1 c.2050G>C mutation. The probands of three families were found to be homozygous for TMC1 c.2050G>C, and their parents were all heterozygous for the TMC1 c.2050G>C mutation. In 110 unrelated patients from Xiamen Special Education School, four were found to carry compound heterozygotes of TMC1 c.2050G>C, which were compound heterozygotes of c.804G>A, c.1127T>C, c.1165C>T, and c.1396_1398delAAC, respectively. Three types of TMC1 polymorphisms (c.45C>T, c.1713C>T, c.2208+49C>T) and two heterozygotes of novel variants (c.1764‐4C>A, c.2073G>A[p.K691K]) were found in the remaining 100 patients. In total, four novel variants were detected in this study. These mutations and variants were not detected in 100 normal samples. The haplotypes of the probands of families with TMC1 c.2050G>C were identical. There were unique hotspots and spectra of TMC1 mutations in the Xiamen deaf population. Haplotype analysis is useful to understand the founder effect of the hot spot mutation.
      PubDate: 2017-11-27T04:50:43.057451-05:
      DOI: 10.1002/ajmg.b.32603
       
  • SLC6A3 polymorphism and response to methylphenidate in children with ADHD:
           A systematic review and meta‐analysis
    • Authors: Robabeh Soleimani; Zivar Salehi, Soheil Soltanipour, Tolou Hasandokht, Mir Mohammad Jalali
      Abstract: Methylphenidate (MPH) is the most commonly used treatment for attention‐deficit hyperactivity disorder (ADHD) in children. However, the response to MPH is not similar in all patients. This meta‐analysis investigated the potential role of SLC6A3 polymorphisms in response to MPH in children with ADHD. Clinical trials or naturalistic studies were selected from electronic databases. A meta‐analysis was conducted using a random‐effects model. Cohen's d effect size and 95% confidence intervals (CIs) were determined. Sensitivity analysis and meta‐regression were performed. Q‐statistic and Egger's tests were conducted to evaluate heterogeneity and publication bias, respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Sixteen studies with follow‐up periods of 1–28 weeks were eligible. The mean treatment acceptability of MPH was 97.2%. In contrast to clinical trials, the meta‐analysis of naturalistic studies indicated that children without 10/10 repeat carriers had better response to MPH (Cohen's d: −0.09 and 0.44, respectively). The 9/9 repeat polymorphism had no effect on the response rate (Cohen's d: −0.43). In the meta‐regression, a significant association was observed between baseline severity of ADHD, MPH dosage, and combined type of ADHD in some genetic models. Sensitivity analysis indicated the robustness of our findings. No publication bias was observed in our meta‐analysis. The GRADE evaluations revealed very low levels of confidence for each outcome of response to MPH. The results of clinical trials and naturalistic studies regarding the effect size between different polymorphisms of SLC6A3 were contradictory. Therefore, further research is recommended.
      PubDate: 2017-11-24T07:26:06.337971-05:
      DOI: 10.1002/ajmg.b.32613
       
  • The role of cadherin genes in five major psychiatric disorders: A
           literature update
    • Authors: Ziarih Hawi; Janette Tong, Callum Dark, Hannah Yates, Beth Johnson, Mark A. Bellgrove
      Abstract: Converging evidence from candidate gene, genome‐wide linkage, and association studies support a role of cadherins in the pathophysiology of five major psychiatric disorders including attention deficit hyperactivity disorder, autism spectrum disorder (ASD), schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). These molecules are transmembrane proteins which act as cell adhesives by forming adherens junctions (AJs) to bind cells within tissues. Members of the cadherin superfamily are also involved in biological processes such as signal transduction and plasticity that have been implicated in the etiology of major psychiatric conditions. Although there are over 110 genes mapped to the cadherin superfamily, our literature survey showed that evidence of association with psychiatric disorders is strongest for CDH7, CHD11, and CDH13. Gene enrichment analysis showed that those cadherin genes implicated in psychiatric disorders were overrepresented in biological processes such as in cell‐cell adhesion (GO:0007156 & GO:0098742) and adherens junction organization (GO:0034332). Further, cadherin genes were also mapped to processes that have been linked to the development of psychiatric disorders such as nervous system development (GO:0007399). To further understand the role of cadherin SNPs implicated in psychiatric disorders, we utilized an in silico computational pipeline to functionally annotate associated variants. This analysis yielded eight variants mapped to PCDH1‐13, CDH7, CDH11, and CDH13 that are predicted to be biologically functional. Functional genomic evaluation is now required to understand the molecular mechanism by which these variants might confer susceptibility to psychiatric disorders.
      PubDate: 2017-09-18T01:55:21.47243-05:0
      DOI: 10.1002/ajmg.b.32592
       
  • The role of CLOCK gene in psychiatric disorders: Evidence from human and
           animal research
    • Authors: Jaqueline B. Schuch; Julia P. Genro, Clarissa R. Bastos, Gabriele Ghisleni, Luciana Tovo-Rodrigues
      Abstract: The circadian clock system drives daily rhythms in physiology, metabolism, and behavior in mammals. Molecular mechanisms of this system consist of multiple clock genes, with Circadian Locomotor Output Cycles Kaput (CLOCK) as a core member that plays an important role in a wide range of behaviors. Alterations in the CLOCK gene are associated with common psychiatric disorders as well as with circadian disturbances comorbidities. This review addresses animal, molecular, and genetic studies evaluating the role of the CLOCK gene on many psychiatric conditions, namely autism spectrum disorder, schizophrenia, attention‐deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, anxiety disorder, and substance use disorder. Many animal experiments focusing on the effects of the Clock gene in behavior related to psychiatric conditions have shown consistent biological plausibility and promising findings. In humans, genetic and gene expression studies regarding disorder susceptibility, sleep disturbances related comorbidities, and response to pharmacological treatment, in general, are in agreement with animal studies. However, the number of controversial results is high. Literature suggests that the CLOCK gene exerts important influence on these conditions, and influences the susceptibility to phenotypes of psychiatric disorders.
      PubDate: 2017-09-13T08:26:26.095757-05:
      DOI: 10.1002/ajmg.b.32599
       
  • Phelan-McDermid syndrome data network: Integrating patient reported
           outcomes with clinical notes and curated genetic reports
    • Authors: Cartik Kothari; Maxime Wack, Claire Hassen-Khodja, Sean Finan, Guergana Savova, Megan O'Boyle, Geraldine Bliss, Andria Cornell, Elizabeth J. Horn, Rebecca Davis, Jacquelyn Jacobs, Isaac Kohane, Paul Avillach
      Abstract: The heterogeneity of patient phenotype data are an impediment to the research into the origins and progression of neuropsychiatric disorders. This difficulty is compounded in the case of rare disorders such as Phelan-McDermid Syndrome (PMS) by the paucity of patient clinical data. PMS is a rare syndromic genetic cause of autism and intellectual deficiency. In this paper, we describe the Phelan-McDermid Syndrome Data Network (PMS_DN), a platform that facilitates research into phenotype–genotype correlation and progression of PMS by: a) integrating knowledge of patient phenotypes extracted from Patient Reported Outcomes (PRO) data and clinical notes—two heterogeneous, underutilized sources of knowledge about patient phenotypes—with curated genetic information from the same patient cohort and b) making this integrated knowledge, along with a suite of statistical tools, available free of charge to authorized investigators on a Web portal https://pmsdn.hms.harvard.edu. PMS_DN is a Patient Centric Outcomes Research Initiative (PCORI) where patients and their families are involved in all aspects of the management of patient data in driving research into PMS. To foster collaborative research, PMS_DN also makes patient aggregates from this knowledge available to authorized investigators using distributed research networks such as the PCORnet PopMedNet. PMS_DN is hosted on a scalable cloud based environment and complies with all patient data privacy regulations. As of October 31, 2016, PMS_DN integrates high-quality knowledge extracted from the clinical notes of 112 patients and curated genetic reports of 176 patients with preprocessed PRO data from 415 patients.
      PubDate: 2017-09-01T06:38:08.481169-05:
      DOI: 10.1002/ajmg.b.32579
       
  • The dopamine transporter role in psychiatric phenotypes
    • Authors: Angélica Salatino-Oliveira; Luis A. Rohde, Mara H. Hutz
      Abstract: The dopamine transporter (DAT) is one of the most relevant and investigated neurotransmitter transporters. DAT is a plasma membrane protein which plays a homeostatic role, controlling both extracellular and intracellular concentrations of dopamine (DA). Since unbalanced DA levels are known to be involved in numerous mental disorders, a wealth of investigations has provided valuable insights concerning DAT role into normal brain functioning and pathological processes. Briefly, this extensive but non-systematic review discusses what is recently known about the role of SLC6A3 gene which encodes the dopamine transporter in psychiatric phenotypes. DAT protein, SLC6A3 gene, animal models, neuropsychology, and neuroimaging investigations are also concisely discussed. To conclude, current challenges are reviewed in order to provide perspectives for future studies.
      PubDate: 2017-08-02T07:20:48.680271-05:
      DOI: 10.1002/ajmg.b.32578
       
  • eHealth provides a novel opportunity to exploit the advantages of the
           Nordic countries in psychiatric genetic research, building on the public
           health care system, biobanks, and registries
    • Authors: Ole A. Andreassen
      Abstract: Nordic countries have played an important role in the recent progress in psychiatric genetics, both with large well–characterized samples and expertise. The Nordic countries have research advantages due to the organization of their societies, including system of personal identifiers, national health registries with information about diseases, treatment and prescriptions, and a public health system with geographical catchment areas. For psychiatric genetic research, the large biobanks and population surveys are a unique added value. Further, the population is motivated to participate in research, and there is a trust in the institutions of the society. These factors have been important for Nordic contributions to biomedical research, and particularly psychiatric genetics. In the era of eHealth, the situation seems even more advantageous for Nordic countries. The system with public health care makes it easy to implement national measures, and most of the Nordic health care sector is already based on electronic information. The potential advantages regarding informed consent, large scale recruitment and follow-up, and longitudinal cohort studies are tremendous. New precision medicine approaches can be tested within the health care system, with an integrated approach, using large hospitals or regions of the country as a test beds. However, data protection and legal framework have to be clarified. In order to succeed, it is important to keep the people's trust, and maintain the high ethical standards and systems for secure data management. Then the full potential of the Nordic countries can be leveraged in the new era of precision medicine including psychiatric genetics.
      PubDate: 2017-07-07T09:25:28.271385-05:
      DOI: 10.1002/ajmg.b.32561
       
  • National-scale precision medicine for psychiatric disorders in Sweden
    • Authors: Sarah E. Bergen; Patrick F. Sullivan
      Abstract: Since psychiatric disorders have genetic architectures dominated by common variants of small effects, successful elucidation in psychiatric genetics necessitates large sample sizes. Collaboration and unconventional ascertainment methods are required to fulfill this need. Electronic health records have been increasingly seen as holding great potential for research, although they often pose substantial technical, legal and ethical challenges. Universal health care and national-scale registers with comprehensive medical, developmental, demographic, and geographic information make the Nordic countries ideal for psychiatric genetic epidemiology. The Genomic Aggregation Project in Sweden is gathering genetic data from subjects with and without complex genetic diseases in a single location for standardized processing and use in a wide variety of scientific investigations. Thirty groups with >160 K genotyped samples have joined GAPS. Although GAPS is general across medicine, many psychiatric disorders are represented within GAPS, and initial studies will focus on major depressive disorder. Through in-depth genetic investigations, the genes and pathways that will be identified can be leveraged for predictive and drug-development purposes. Sweden offers exceptional possibilities for psychiatric genetics, and GAPS aims to harness the wealth of available information for research to improve human health.
      PubDate: 2017-07-07T09:25:24.072131-05:
      DOI: 10.1002/ajmg.b.32562
       
  • A comprehensive review of the genetic and biological evidence supports a
           role for MicroRNA-137 in the etiology of schizophrenia
    • Authors: Kensuke Sakamoto; James J. Crowley
      Abstract: Since it was first associated with schizophrenia (SCZ) in a 2011 genome-wide association study (GWAS), there have been over 100 publications focused on MIR137, the gene encoding microRNA-137. These studies have examined everything from its fundamental role in the development of mice, flies, and fish to the intriguing enrichment of its target gene network in SCZ. Indeed, much of the excitement surrounding MIR137 is due to the distinct possibility that it could regulate a gene network involved in SCZ etiology, a disease which we now recognize is highly polygenic. Here we comprehensively review, to the best of our ability, all published genetic and biological evidence that could support or refute a role for MIR137 in the etiology of SCZ. Through a careful consideration of the literature, we conclude that the data gathered to date continues to strongly support the involvement of MIR137 and its target gene network in neuropsychiatric traits, including SCZ risk. There remain, however, more unanswered than answered questions regarding the mechanisms linking MIR137 genetic variation with behavior. These questions need answers before we can determine whether there are opportunities for diagnostic or therapeutic interventions based on MIR137. We conclude with a number of suggestions for future research on MIR137 that could help to provide answers and hope for a greater understanding of this devastating disorder.
      PubDate: 2017-06-14T21:25:25.152392-05:
      DOI: 10.1002/ajmg.b.32554
       
  • Association between COMT Val158Met and psychiatric disorders: A
           comprehensive meta-analysis
    • Authors: Steven Taylor
      Abstract: Catechol-O-methyltransferase (COMT) Val158Met is widely regarded as potentially important for understanding the genetic etiology of many different psychiatric disorders. The present study appears to be the first comprehensive meta-analysis of COMT genetic association studies to cover all psychiatric disorders for which there were available data, published in any language, and with an emphasis on investigating disorder subtypes (defined clinically or by demographic or other variables). Studies were included if they reported one or more datasets (i.e., some studies examined more than one clinical group) in which there were sufficient information to compute effect sizes. A total of 363 datasets were included, consisting of 56,998 cases and 74,668 healthy controls from case control studies, and 2,547 trios from family based studies. Fifteen disorders were included. Attention-deficit hyperactivity disorder and panic disorder were associated with the Val allele for Caucasian samples. Substance-use disorder, defined by DSM-IV criteria, was associated with the Val allele for Asian samples. Bipolar disorder was associated with the Met allele in Asian samples. Obsessive-compulsive disorder tended to be associated with the Met allele only for males. There was suggestive evidence that the Met allele is associated with an earlier age of onset of schizophrenia. Results suggest pleiotropy and underscore the importance of examining subgroups—defined by variables such as age of onset, sex, ethnicity, and diagnostic system—rather than examining disorders as monolithic constructs.
      PubDate: 2017-06-13T07:10:25.985587-05:
      DOI: 10.1002/ajmg.b.32556
       
  • The use of electronic health records for psychiatric phenotyping and
           genomics
    • Authors: Jordan W. Smoller
      Abstract: The widespread adoption of electronic health record (EHRs) in healthcare systems has created a vast and continuously growing resource of clinical data and provides new opportunities for population-based research. In particular, the linking of EHRs to biospecimens and genomic data in biobanks may help address what has become a rate-limiting study for genetic research: the need for large sample sizes. The principal roadblock to capitalizing on these resources is the need to establish the validity of phenotypes extracted from the EHR. For psychiatric genetic research, this represents a particular challenge given that diagnosis is based on patient reports and clinician observations that may not be well-captured in billing codes or narrative records. This review addresses the opportunities and pitfalls in EHR-based phenotyping with a focus on their application to psychiatric genetic research. A growing number of studies have demonstrated that diagnostic algorithms with high positive predictive value can be derived from EHRs, especially when structured data are supplemented by text mining approaches. Such algorithms enable semi-automated phenotyping for large-scale case-control studies. In addition, the scale and scope of EHR databases have been used successfully to identify phenotypic subgroups and derive algorithms for longitudinal risk prediction. EHR-based genomics are particularly well-suited to rapid look-up replication of putative risk genes, studies of pleiotropy (phenomewide association studies or PheWAS), investigations of genetic networks and overlap across the phenome, and pharmacogenomic research. EHR phenotyping has been relatively under-utilized in psychiatric genomic research but may become a key component of efforts to advance precision psychiatry.
      PubDate: 2017-05-30T05:30:32.510304-05:
      DOI: 10.1002/ajmg.b.32548
       
  • The highly pleiotropic gene SLC39A8 as an opportunity to gain insight into
           the molecular pathogenesis of schizophrenia
    • Authors: Javier Costas
      Abstract: There is a long way from the initial discovery of a genome-wide significant signal to mechanistic understanding of the association. Identification of the gene and causal polymorphism usually requires an extensive additional effort. The schizophrenia genome-wide significant locus at 4q24 may be a rare exception to this pattern. As discussed in this review, the association at this locus is most probably driven by a functional missense variant at the metal cations transporter SLC39A8. The variant, rs13107325, is almost exclusive of European populations and is one of the most pleiotropic variants of the genome, being associated at genome-wide significant level with several additional traits, such as body mass index, Crohn's disease, blood pressure related-traits, and serum levels of manganese, N-terminal pro-B-type natriuretic peptide and HDL-cholesterol. SLC39A8 seems to be subject to recent natural selection in Europeans. It is almost ubiquitously expressed and its physiological role is beginning to be elucidated, mainly in relation to immunity. This manuscript presents arguments in favor of the rs13107325 variant as the functional variant responsible for the association of this locus with schizophrenia, reviews the genetic associations with this gene, the evidences of natural selection on the gene, and the known aspects about its structure and physiological functions. Finally, some hypotheses about putative mechanisms for its association with schizophrenia are presented based on this knowledge, including impaired immunity/inflammation, interference with glutamatergic neurotransmission, homeostasis of essential metals in brain, such as iron, zinc or manganese, or neurotoxicity by heavy metals, such as cadmium or lead.
      PubDate: 2017-05-30T05:30:28.912967-05:
      DOI: 10.1002/ajmg.b.32545
       
  • Neuregulin 3 and its roles in schizophrenia risk and presentation
    • Authors: Dimitrios Avramopoulos
      Abstract: Neuregulins, a four-member family of epidermal growth factor-like signaling molecules, have been studied for over two decades. They were first implicated in schizophrenia in 2002 with the detection of linkage and association at the NRG1 locus followed after a few years by NRG3. However, the associations with disease have not been very consistently observed. In contrast, association of NGR3 variants with disease presentation, specifically the presence of delusions, has been more consistent. This appears to be mediated by quantitative changes in the alternative splicing of the gene, which has also been consistently observed. Additional diseases and phenotypes, psychiatric or not, have also been connected with NRG3. These results demonstrate two important aspects of behavioral genetics research. The first is that if we only consider simple risk and fail to examine the details of each patient's individual phenotype, we will miss important insights on the disease biology. This is an important aspect of the goals of precision medicine. The second is that the functional consequences of variants are often more complex than simple alterations in levels of transcription of a particular gene, including, among others, regulation of alternative splicing. To accurately model and understand the biological consequences of phenotype—associated genetic variants, we need to study the biological consequences of each specific variant. Simply studying the consequences of a null allele of the orthologous gene in a model system, runs the risk of missing the many nuances of hypomorphic and/or gain of function variants in the genome of interest.
      PubDate: 2017-05-29T06:30:38.495294-05:
      DOI: 10.1002/ajmg.b.32552
       
  • Glucocerebrosidase mutations and neuropsychiatric phenotypes in
           Parkinson's disease and Lewy body dementias: Review and meta-analyses
    • Authors: Byron Creese; Emily Bell, Iskandar Johar, Paul Francis, Clive Ballard, Dag Aarsland
      Abstract: Heterozygous mutations in glucocerebrosidase gene (GBA) are a major genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, there has been a considerable focus on the relationship between GBA mutations and emergence of cognitive impairment and neuropsychiatric symptoms in these diseases. Here, we review the literature in this area, with a particular focus, including meta-analysis, on the key neuropsychiatric symptoms of cognitive impairment, psychosis, and depression in Parkinson's disease. Our meta-analysis demonstrated that GBA mutations are associated with a 2.4-fold increased risk of cognitive impairment. In addition, our novel meta-analyses of psychosis and depression showed a 1.8- and 2.2-fold increased risk respectively associated with GBA mutations, although due to possible bias and heterogeneity the depression findings should be interpreted with caution. While the precise mechanisms which increase susceptibility to neurodegeneration in GBA carriers are not known, evidence of greater cortical Lewy body pathology, reduced patterns of cortical activation, and hippocampal pathology in animal models are all consistent with a direct effect of GBA mutations on these symptoms. Extension of this work in DLB and individuals without neurodegeneration will be important in further characterizing how GBA mutations increase risk for PD and DLB and influence disease course.
      PubDate: 2017-05-26T07:40:38.922895-05:
      DOI: 10.1002/ajmg.b.32549
       
  • A gene-based review of RGS4 as a putative risk gene for psychiatric
           illness
    • Authors: Emanuel Schwarz
      Abstract: Considerable efforts have been made to characterize RGS4 as a potential candidate gene for schizophrenia. Investigations span across numerous modalities and include explorations of genetic risk associations, mRNA and protein levels in the brain, and functionally relevant interactions with other candidate genes as well as links to schizophrenia relevant neural phenotypes. While these lines of investigations have yielded partially inconsistent findings, they provide a perspective on RGS4 as an important part of a larger biological system contributing to schizophrenia risk. This gene-based review aims to provide a comprehensive overview of published data from different experimental modalities and discusses the current knowledge of RGS4's systems-biological impact on the schizophrenia pathology.
      PubDate: 2017-05-24T23:35:45.568894-05:
      DOI: 10.1002/ajmg.b.32547
       
  • ADH1B: From alcoholism, natural selection, and cancer to the human phenome
    • Authors: Renato Polimanti; Joel Gelernter
      Abstract: The ADH1B (Alcohol Dehydrogenase 1B (class I), Beta Polypeptide) gene and its best-known functional alleles, Arg48His (rs1229984, ADH1B*2) and Arg370Cys (rs2066702, ADH1B*3), have been investigated in relation to many phenotypic traits; most frequently including alcohol metabolism and alcohol drinking behaviors, but also human evolution, liver function, cancer, and, recently, the comprehensive human phenome. To understand ADH1B functions and consequences, we provide here a bioinformatic analysis of its gene regulation and molecular functions, literature review of studies focused on this gene, and a discussion regarding future research perspectives. Certain ADH1B alleles have large effects on alcohol metabolism, and this relationship particularly encourages further investigations in relation to alcoholism and alcohol-associated cancer to understand better the mechanisms by which alcohol metabolism contributes to alcohol abuse and carcinogenesis. We also observed that ADH1B has complex mechanisms that regulate its expression across multiple human tissues, and these may be involved in cardiac and metabolic traits. Evolutionary data strongly suggest that the selection signatures at the ADH1B locus are primarily related to effects other than those on alcohol metabolism. This is also supported by the involvement of ADH1B in multiple molecular pathways and by the findings of our recent phenome-wide association study. Accordingly, future studies should also investigate other functions of ADH1B potentially relevant for the human phenome. © 2017 Wiley Periodicals, Inc.
      PubDate: 2017-03-27T23:45:27.580028-05:
      DOI: 10.1002/ajmg.b.32523
       
  • Issue Information ‐ TOC
    • First page: 1
      PubDate: 2017-12-12T09:58:40.067193-05:
      DOI: 10.1002/ajmg.b.32584
       
  • Association study of NDST3 gene for schizophrenia, bipolar disorder, major
           depressive disorder in the Han Chinese population
    • Authors: Lin Wang; Jianhua Chen, Zhiqiang Li, Weiming Sun, Boyu Chen, Sining Li, Weidong Li, Dajiang Lu, Yonggang Wang, Yongyong Shi
      First page: 3
      Abstract: The NDST3 gene at 4q26 was a functional candidate gene for mental disorders. Recently, a novel genome‐wide significant risk locus at chromosome 4q26 was identified and the top single nucleotide polymorphism rs11098403 in the vicinity of NDST3 gene was reported to confer risk of schizophrenia in Caucasian. Nevertheless, association between NDST3 gene polymorphisms and schizophrenia, bipolar disorder, or major depressive disorders has not been well studied in the Han Chinese population. To further investigate whether NDST3 is a risk gene for these mental disorders, we genotyped and analyzed eight tag SNPs (rs11098403, rs10857057, rs2389521, rs4833564, rs6837896, rs7689157, rs3817274, rs609512) covering NDST3 gene in 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls of Chinese origin. However, there was no significant difference in allelic or genotypic frequency observed between each case group and healthy controls. Accordingly, our study does not support that the NDST3 gene plays a major role in schizophrenia, bipolar disorder, and major depressive disorder in the Han Chinese population.
      PubDate: 2017-11-15T10:01:03.164196-05:
      DOI: 10.1002/ajmg.b.32573
       
  • Exome sequencing reveals NAA15 and PUF60 as candidate genes associated
           with intellectual disability
    • Authors: Jin J. Zhao; Jonatan Halvardson, Cecilia S. Zander, Ammar Zaghlool, Patrik Georgii-Hemming, Else Månsson, Göran Brandberg, Helena E. Sävmarker, Carina Frykholm, Ekaterina Kuchinskaya, Ann-Charlotte Thuresson, Lars Feuk
      First page: 10
      Abstract: Intellectual Disability (ID) is a clinically heterogeneous condition that affects 2–3% of population worldwide. In recent years, exome sequencing has been a successful strategy for studies of genetic causes of ID, providing a growing list of both candidate and validated ID genes. In this study, exome sequencing was performed on 28 ID patients in 27 patient‐parent trios with the aim to identify de novo variants (DNVs) in known and novel ID associated genes. We report the identification of 25 DNVs out of which five were classified as pathogenic or likely pathogenic. Among these, a two base pair deletion was identified in the PUF60 gene, which is one of three genes in the critical region of the 8q24.3 microdeletion syndrome (Verheij syndrome). Our result adds to the growing evidence that PUF60 is responsible for the majority of the symptoms reported for carriers of a microdeletion across this region. We also report variants in several genes previously not associated with ID, including a de novo missense variant in NAA15. We highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain, the fact that the gene is highly intolerant to loss of function and coding variation, and previously reported DNVs in neurodevelopmental disorders.
      PubDate: 2017-10-09T01:20:55.214006-05:
      DOI: 10.1002/ajmg.b.32574
       
  • A polygenic risk score analysis of psychosis endophenotypes across brain
           functional, structural, and cognitive domains
    • Authors: Siri Ranlund; Stella Calafato, Johan H. Thygesen, Kuang Lin, Wiepke Cahn, Benedicto Crespo-Facorro, Sonja M.C. de Zwarte, Álvaro Díez, Marta Di Forti, , Conrad Iyegbe, Assen Jablensky, Rebecca Jones, Mei-Hua Hall, Rene Kahn, Luba Kalaydjieva, Eugenia Kravariti, Colm McDonald, Andrew M. McIntosh, Andrew McQuillin, , Marco Picchioni, Diana P. Prata, Dan Rujescu, Katja Schulze, Madiha Shaikh, Timothea Toulopoulou, Neeltje van Haren, Jim van Os, Evangelos Vassos, Muriel Walshe, , Cathryn Lewis, Robin M. Murray, John Powell, Elvira Bramon
      First page: 21
      Abstract: This large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N = 515), lateral ventricular volume (N = 798), and the cognitive measures block design (N = 3,089), digit span (N = 1,437), and the Ray Auditory Verbal Learning Task (N = 2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p = 0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p = 0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p = 0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.
      PubDate: 2017-08-29T06:40:31.850403-05:
      DOI: 10.1002/ajmg.b.32581
       
  • Predictive testing of minors for Huntington's disease: The UK and
           Netherlands experiences
    • Authors: Oliver W. Quarrell; Angus J. Clarke, Cecilia Compton, Christine E.M. de Die-Smulders, Alan Fryer, Sian Jenkins, Nayana Lahiri, Rhona MacLeod, Zosia Miedzybrodzka, Patrick J. Morrison, Hannah Musgrave, Mary O'Driscoll, Mark Strong, Martine J. van Belzen, Sascha Vermeer, Corien C. Verschuuren-Bemelmans, Emilia K. Bijlsma
      First page: 35
      Abstract: A consistent feature of predictive testing guidelines for Huntington's disease (HD) is the recommendation not to undertake predictive tests on those
      PubDate: 2017-11-02T08:15:21.937501-05:
      DOI: 10.1002/ajmg.b.32582
       
  • Genome‐wide gene‐environment interaction in depression: A systematic
           evaluation of candidate genes
    • Authors: Sandra Van der Auwera; Wouter J. Peyrot, Yuri Milaneschi, Johannes Hertel, Bernhard Baune, Gerome Breen, Enda Byrne, Erin C. Dunn, Helen Fisher, Georg Homuth, Douglas Levinson, Cathryn Lewis, Natalie Mills, Niamh Mullins, Matthias Nauck, Giorgio Pistis, Martin Preisig, Marcella Rietschel, Stephan Ripke, Patrick Sullivan, Alexander Teumer, Henry Völzke, , Dorret I. Boomsma, Naomi R. Wray, Brenda Penninx, Hans Grabe
      First page: 40
      Abstract: Gene by environment (GxE) interaction studies have investigated the influence of a number of candidate genes and variants for major depressive disorder (MDD) on the association between childhood trauma and MDD. Most of these studies are hypothesis driven and investigate only a limited number of SNPs in relevant pathways using differing methodological approaches. Here (1) we identified 27 genes and 268 SNPs previously associated with MDD or with GxE interaction in MDD and (2) analyzed their impact on GxE in MDD using a common approach in 3944 subjects of European ancestry from the Psychiatric Genomics Consortium who had completed the Childhood Trauma Questionnaire. (3) We subsequently used the genome‐wide SNP data for a genome‐wide case‐control GxE model and GxE case‐only analyses testing for an enrichment of associated SNPs. No genome‐wide significant hits and no consistency among the signals of the different analytic approaches could be observed. This is the largest study for systematic GxE interaction analysis in MDD in subjects of European ancestry to date. Most of the known candidate genes/variants could not be supported. Thus, their impact on GxE interaction in MDD may be questionable. Our results underscore the need for larger samples, more extensive assessment of environmental exposures, and greater efforts to investigate new methodological approaches in GxE models for MDD.
      PubDate: 2017-11-21T00:35:37.91151-05:0
      DOI: 10.1002/ajmg.b.32593
       
  • Contribution of genes in the GABAergic pathway to bipolar disorder and its
           executive function deficit in the Chinese Han population
    • Authors: Hongyan Ren; Lijie Guan, Liansheng Zhao, Yin Lin, Yincheng Wang, Zhenxing Yang, Xuan Li, Xiaohong Ma, Xiongchao Cheng, Wenhao Deng, Katherine J. Aitchison, Liping Cao, Tao Li
      First page: 50
      Abstract: In this study, we investigated the association between bipolar I disorder (BDI) and between cognitive deficits therein and SNPs in GABAergic receptor genes. The sample comprised 477 patients with BDI and 438 healthy controls, with three neurocognitive tests being administered in 123 patients and 164 controls. For three SNPs, rs505474, rs1398175, and rs4868029 in the GABRA2, GABRA4, and GABRP genes, respectively, their allele frequencies were significantly different between patients and controls (Bonferroni‐adjusted p = values 3.84 × 10−4, 9.92 × 10−3, and 1.22 × 10−2, respectively). Four haplotypes were significantly associated with BDI (TA and AG for rs3815762 and rs4868029 in GABRP, GG for rs11636988 and rs8024256 in GABRB3 and GAGG for rs2197414, rs4921195, rs13188991, and rs11956731 in GABRA6, with p values of 0.0038, 0.044, 0.0176, and 0.0267, respectively, on 10,000 permutations). Furthermore, the SNP (rs2912585) within 250 kb upstream of the GABRB3 gene displayed a strong association with the Tower of Hanoi (TOH) executive time in the patient group (p = 2.844 × 10−6). One other SNP (rs754661), which is located at the intronic region of the same gene, was associated with the global trait of the executive function and post hoc analysis showed significant SNP by group effect (p = 0.0094). Our study supports previous findings that GABAA receptor genes are associated with bipolar disorder; it also suggests that the GABAA genes, especially the GABRB3 gene, might play a role in the executive function deficit in bipolar disorder, although future replication with a larger sample size is needed.
      PubDate: 2017-11-14T08:15:43.201182-05:
      DOI: 10.1002/ajmg.b.32601
       
  • Estimation of minimal disease prevalence from population genomic data:
           Application to primary familial brain calcification
    • Authors: Gaël Nicolas; Camille Charbonnier, Dominique Campion, Joris A. Veltman
      First page: 68
      Abstract: Primary Familial Brain Calcification (PFBC) is a rare calcifying disorder of the brain with autosomal dominant inheritance, of unknown prevalence. Four causal genes have been identified so far: SLC20A2, PDGFB, PDGFRB, and XPR1, with pathogenic, probably pathogenic or missense variants of unknown significance found in 27.7% probands in the French PFBC series. Estimating PFBC prevalence from a clinical input is arduous due to a large diversity of symptoms and ages of onset and to incomplete clinical penetrance. Abnormal calcifications on CT scan can be used as a reliable diagnostic biomarker whatever the clinical status, but differential diagnoses should be ruled out including the challenging exclusion of common basal ganglia calcifications. Our primary aim was to estimate the minimal prevalence of PFBC due to a variant in one of the known genes. We extracted variants from the four known genes present in the gnomAD database gathering genomic data from 138,632 individuals. We interpreted all variants based on their predicted effect, their frequency, and previous studies on PFBC patients. Using the most conservative estimate, the minimal prevalence of PFBC related to a variant in one of the four known genes was 4.5 p. 10,000 (95%CI [3.4–5.5] p. 10,000). We then used variant detection rates in patients to extrapolate an overall minimal prevalence of PFBC to 2.1 p. 1,000 (95%CI [1.9–2.4] p. 1,000). The population‐based genomic analysis indicates that PFBC is not an exceptionally rare disorder, still underestimated and underdiagnosed.
      PubDate: 2017-11-20T01:05:37.943841-05:
      DOI: 10.1002/ajmg.b.32605
       
  • OPTN p.Met468Arg and ATXN2 intermediate length polyQ extension in families
           with C9orf72 mediated amyotrophic lateral sclerosis and frontotemporal
           dementia
    • Authors: Sali M. K. Farhan; Tania F. Gendron, Leonard Petrucelli, Robert A. Hegele, Michael J. Strong
      First page: 75
      Abstract: We have ascertained two families affected with familial amyotrophic lateral sclerosis (ALS) in which they both carry a hexanucleotide repeat expansion in the C9orf72 gene, specifically in individuals who also presented with frontotemporal dementia (FTD) or behavioral variant FTD (bvFTD). While some reports attribute this phenotypic heterogeneity to the C9orf72 expansion alone, we screened for additional genetic variation in known ALS‐FTD genes that may also contribute to or modify the phenotypes. We performed genetic testing consisting of C9orf72 hexanucleotide expansion, ATXN2 polyglutamine (polyQ) expansion, and targeted next generation sequencing using the ONDRISeq, a gene panel consisting of 80 genes known to be associated with neurodegenerative diseases such as ALS, FTD, Alzheimer's disease, Parkinson's disease, and vascular cognitive impairment. In addition to the C9orf72 expansion, we observed an ATXN2 polyQ intermediate length expansion, and OPTN p.Met468Arg in patients who exhibited ALS and FTD or bvFTD. We conclude that the C9orf72 expansion likely explains much of the ALS‐FTD phenotype; however, inheritance of these additional variants likely modifies the disease course and may provide further evidence for biologically relevant oligogenic inheritance in ALS.
      PubDate: 2017-10-28T06:25:29.00188-05:0
      DOI: 10.1002/ajmg.b.32606
       
  • Genetic overlap between epilepsy and schizophrenia: Evidence from cross
           phenotype analysis in Hong Kong Chinese population
    • Authors: Hongsheng Gui; Miaoxin Li, Pak C. Sham, Larry Baum, , Patrick Kwan, Stacey S. Cherny
      First page: 86
      Abstract: Epilepsy and schizophrenia are common and typical neurological or mental illness respectively, and sometimes they comorbid in the same patients, however the underlying genetic relationship between the two brain diseases is still not fully understood. To investigate the possible genetic contribution to their comorbidity, we performed polygenic risk score (PRS) analyses and genetic correlation estimation so as to identify the overall genetic overlap between the two diseases. The global schizophrenia PRS is strongly associated with schizophrenia phenotype in Hong Kong population (odds ratio = 1.7, p = 2.26E‐16), and focal epilepsy PRS is moderately associated with epilepsy phenotype in Hong Kong population (odds ratio = 1.14, p = 0.013). However the disease‐specific PRS can only predict its own well‐matched phenotype but not the other ones (p > 0.05). This pattern is further supported by non‐significant pairwise genetic correlation and insufficient statistical power for PRS association from the cross‐phenotype analyses. Our study reveals there's limited shared genetic aetiology between schizophrenia and epilepsy, and thus supports a model of shared environmental factors to explain the comorbidity between the two phenotypes.
      PubDate: 2017-11-17T21:25:31.157478-05:
      DOI: 10.1002/ajmg.b.32607
       
  • Association of IMMP2L deletions with autism spectrum disorder: A trio
           family study and meta‐analysis
    • Authors: Yanqing Zhang; Yi Liu, Mehdi Zarrei, Winnie Tong, Rui Dong, Ying Wang, Haiyan Zhang, Xiaomeng Yang, Jeffrey R. MacDonald, Mohammed Uddin, Stephen W. Scherer, Zhongtao Gai
      First page: 93
      Abstract: IMMP2L, the gene encoding the inner mitochondrial membrane peptidase subunit 2‐like protein, has been reported as a candidate gene for Tourette syndrome, autism spectrum disorder (ASD) and additional neurodevelopmental disorders. Here we genotyped 100 trio families with an index proband with autism spectrum disorder in Han Chinese population and found three cases with rare exonic IMMP2L deletions. We have conducted a comprehensive meta‐analysis to quantify the association of IMMP2L deletions with ASD using 5,568 cases and 10,279 controls. While the IMMP2L deletions carried non‐recurrent breakpoints, in contrast to previous reports, our meta‐analysis found no evidence of association (P > 0.05) between IMMP2L deletions and ASD. We also observed common exonic deletions impacting IMMP2L in a separate control (5,971 samples) cohort where subjects were screened for psychiatric conditions. This is the first systematic review and meta‐analysis regarding the effect of IMMP2L deletions on ASD, but further investigations in different populations, especially Chinese population may be still needed to confirm our results.
      PubDate: 2017-11-20T01:05:30.217741-05:
      DOI: 10.1002/ajmg.b.32608
       
  • Broad spectrum of neuropsychiatric phenotypes associated with white matter
           disease in PTEN hamartoma tumor syndrome
    • Authors: Tugce B. Balci; Jorge Davila, Denice Lewis, Addo Boafo, Erick Sell, Julie Richer, Sarah M. Nikkel, Christine M. Armour, Eva Tomiak, Matthew A. Lines, Sarah L. Sawyer
      First page: 101
      Abstract: White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN‐related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals.
      PubDate: 2017-11-20T01:05:40.901636-05:
      DOI: 10.1002/ajmg.b.32610
       
  • APOE gene and neuropsychiatric disorders and endophenotypes: A
           comprehensive review
    • Authors: Diego A. Forero; Sandra López-León, Yeimy González-Giraldo, Daniel R. Dries, Angela J. Pereira-Morales, Karen M. Jiménez, Juan E. Franco-Restrepo
      Abstract: The Apolipoprotein E (APOE) gene is one of the main candidates in neuropsychiatric genetics, with hundreds of studies carried out in order to explore the possible role of polymorphisms in the APOE gene in a large number of neurological diseases, psychiatric disorders, and related endophenotypes. In the current article, we provide a comprehensive review of the structural and functional aspects of the APOE gene and its relationship with brain disorders. Evidence from genome-wide association studies and meta-analyses shows that the APOE gene has been significantly associated with several neurodegenerative disorders. Cellular and animal models show growing evidence of the key role of APOE in mechanisms of brain plasticity and behavior. Future analyses of the APOE gene might find a possible role in other neurological diseases and psychiatric disorders and related endophenotypes. © 2016 Wiley Periodicals, Inc.
      PubDate: 2016-12-12T00:01:11.234013-05:
      DOI: 10.1002/ajmg.b.32516
       
 
 
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