@article{64289c8c0de544079542d9b000c66e9f,
title = "Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability",
abstract = "The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h 2 SNP) for European-American females of 29% that is similar to h 2 SNP for schizophrenia and is substantially higher than h 2 SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD - for both European- and African-American individuals - and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for 1/410 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.",
author = "Duncan, {L. E.} and A. Ratanatharathorn and Aiello, {A. E.} and Almli, {L. M.} and Amstadter, {A. B.} and Ashley-Koch, {A. E.} and Baker, {D. G.} and Beckham, {J. C.} and Bierut, {L. J.} and J. Bisson and B. Bradley and Chen, {C. Y.} and S. Dalvie and Farrer, {L. A.} and S. Galea and Garrett, {M. E.} and Gelernter, {J. E.} and G. Guffanti and Hauser, {M. A.} and Johnson, {E. O.} and Kessler, {R. C.} and Kimbrel, {N. A.} and A. King and N. Koen and Kranzler, {H. R.} and Logue, {M. W.} and Maihofer, {A. X.} and Martin, {A. R.} and Miller, {M. W.} and Morey, {R. A.} and Nugent, {N. R.} and Rice, {J. P.} and S. Ripke and Roberts, {A. L.} and Saccone, {N. L.} and Smoller, {J. W.} and Stein, {D. J.} and Stein, {M. B.} and Sumner, {J. A.} and M. Uddin and Ursano, {R. J.} and Wildman, {D. E.} and R. Yehuda and H. Zhao and Daly, {M. J.} and I. Liberzon and Ressler, {K. J.} and Nievergelt, {C. M.} and Koenen, {K. C.}",
note = "Funding Information: We thank study participants and research groups contributing to PGC-PTSD for sharing their data and their time to make this work possible. We thank One Mind (LED), Cohen Veterans Bioscience (LED and PGC-PTSD group) and the Stanley Center for Psychiatric Research for their financial support. Analysis and other work on this project was supported by 3U01MH094432-03S1 (MJD) and 5U01MH094432-04 (MJD). Finally, we acknowledge Steve Hyman of the Stanley Center for Psychiatric Research and Harvard University for comments on various versions of this manuscript. For study-specific acknowledgments, see Supplementary Information. Funding Information: Dr Kranzler has been an advisory board member, consultant or CME speaker for Indivior, Lundbeck and Otsuka. He is also a member of the American Society of Clinical Psychopharmacology{\textquoteright}s Alcohol Clinical Trials Initiative that is supported by AbbVie, Alkermes, Ethypharm, Indivior, Lilly, Lundbeck, Otsuka, Pfizer and XenoPort. Dr Ressler is a founding member of Extinction Pharmaceuticals to develop D-Cycloserine to augment the effectiveness of psychotherapy. He has received no equity or income from this relationship within the past 3 years. Dr Ressler is also on the Scientific Advisory Boards for Resilience Therapeutics, Sheppard Pratt-Lieber Research Institute, Laureate Institute for Brain Research, The Army STARRS Project and the Anxiety and Depression Association of America. He holds patents for use of D-cycloserine and psychotherapy, targeting PAC1 receptor for extinction, targeting tachykinin 2 for prevention of fear and targeting angiotensin to improve extinction of fear. He receives or has received research funding from NIMH, HHMI, NARSAD, and the Burroughs Wellcome Foundation. In the past 3 years, Dr Dan J Stein has received research grants and/or consultancy honoraria from AMBRF, Biocodex, Cipla, Lundbeck, National Responsible Gambling Foundation, Novartis, Servier and Sun. Dr Murray Stein reports receiving in the past 3 years consultant fees from Actelion, Janssen, Dart Neuroscience, Healthcare Management Technologies and Pfizer. He also has an equity interest in Resilience Therapeutics and Oxeia Biopharmaceuticals. He has also received editorial honoraria from Biological Psychiatry and Up-To-Date. Dr Bierut is listed as an inventor on Issued US Patent 8,080,371, {\textquoteleft}Markers for Addiction{\textquoteright} covering the use of certain SNPs in determining the diagnosis, prognosis and treatment of addiction. In the past 3 years, Dr Kessler received support for his epidemiological studies from Sanofi Aventis; was a consultant for Johnson & Johnson Wellness and Prevention, Shire and Takeda; and has served on an advisory board for the Johnson & Johnson Services Lake Nona Life Project. Kessler is a co-owner of DataStat, a market research firm that carries out health-care research. In the past 3 years, Dr Liberzon has been a consultant for ARMGO Pharmaceutical, Sunovion Pharmaceutical and Trimaran Pharma. The remaining authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} The Author(s) 2018.",
year = "2018",
month = mar,
day = "1",
doi = "10.1038/mp.2017.77",
language = "English",
volume = "23",
pages = "666--673",
journal = "Molecular Psychiatry",
issn = "1359-4184",
number = "3",
}