Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability
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...
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| Published in: | Molecular psychiatry Vol. 23; no. 3; p. 666 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Nature Publishing Group
01.03.2018
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| Subjects: | |
| ISSN: | 1359-4184, 1476-5578, 1476-5578 |
| Online Access: | Get full text |
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| 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
) for European-American females of 29% that is similar to h
for schizophrenia and is substantially higher than h
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 ∼10 000 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. |
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| AbstractList | 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
) for European-American females of 29% that is similar to h
for schizophrenia and is substantially higher than h
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 ∼10 000 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. 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 (h2 SNP ) for European-American females of 29% that is similar to h2 SNP for schizophrenia and is substantially higher than h2 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 ∼10 000 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. 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 (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP 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 ∼10 000 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.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 (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP 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 ∼10 000 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 | Bisson, J Rice, J P Ressler, K J Morey, R A Daly, M J Koen, N Sumner, J A Maihofer, A X Nugent, N R Kimbrel, N A Miller, M W Baker, D G Zhao, H Saccone, N L Duncan, L E Ratanatharathorn, A Gelernter, J E Stein, D J Roberts, A L Kessler, R C Kranzler, H R Martin, A R Ursano, R J Hauser, M A Liberzon, I Bradley, B Logue, M W Garrett, M E Chen, C-Y Farrer, L A Amstadter, A B Almli, L M Beckham, J C Dalvie, S Uddin, M Ripke, S Yehuda, R Ashley-Koch, A E Guffanti, G Smoller, J W Galea, S King, A Bierut, L J Aiello, A E Johnson, E O Stein, M B Wildman, D E Koenen, K C Nievergelt, C M |
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Department of Psychiatry, Harvard University, Cambridge, MA, USA – sequence: 13 givenname: S surname: Dalvie fullname: Dalvie, S organization: Division of Human Genetics, University of Cape Town, Cape Town, South Africa – sequence: 14 givenname: L A surname: Farrer fullname: Farrer, L A organization: Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA – sequence: 15 givenname: S surname: Galea fullname: Galea, S organization: Boston University School of Public Health, Boston, MA, USA – sequence: 16 givenname: M E surname: Garrett fullname: Garrett, M E organization: Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA – sequence: 17 givenname: J E surname: Gelernter fullname: Gelernter, J E organization: Department of Psychiatry, Yale University School of Medicine and VA CT Healthcare System, New Haven, CT, USA – sequence: 18 givenname: G surname: Guffanti fullname: Guffanti, G organization: Department of Psychiatry, McLean Hospital, Belmont, MA, USA – sequence: 19 givenname: M A orcidid: 0000-0003-2667-5420 surname: Hauser fullname: Hauser, M A organization: Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA – sequence: 20 givenname: E O surname: Johnson fullname: Johnson, E O organization: RTI International, Research Triangle Park, NC, USA – sequence: 21 givenname: R C surname: Kessler fullname: Kessler, R C organization: Department of Health Care Policy, Harvard Medical School, Boston, MA, USA – sequence: 22 givenname: N A surname: Kimbrel fullname: Kimbrel, N A organization: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA – sequence: 23 givenname: A surname: King fullname: King, A organization: Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA – sequence: 24 givenname: N surname: Koen fullname: Koen, N organization: MRC Unit on Anxiety & Stress Disorders, 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Chan School of Public Health Cambridge, MA, USA – sequence: 35 givenname: N L surname: Saccone fullname: Saccone, N L organization: Department of Genetics, Washington University, St Louis, MO, USA – sequence: 36 givenname: J W surname: Smoller fullname: Smoller, J W organization: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA – sequence: 37 givenname: D J surname: Stein fullname: Stein, D J organization: MRC Unit on Anxiety & Stress Disorders, Groote Schuur Hospital, Cape Town, South Africa – sequence: 38 givenname: M B surname: Stein fullname: Stein, M B organization: Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA – sequence: 39 givenname: J A surname: Sumner fullname: Sumner, J A organization: Center for Cardiovascular Behavioral Health, Columbia University Medical Center, New York, NY, USA – sequence: 40 givenname: M surname: Uddin fullname: Uddin, M organization: Department of Psychology and Carl R. 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Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA – sequence: 43 givenname: R surname: Yehuda fullname: Yehuda, R organization: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, Bronx, NY, USA – sequence: 44 givenname: H surname: Zhao fullname: Zhao, H organization: Department of Biostatistics, Yale University, New Haven, CT, USA – sequence: 45 givenname: M J orcidid: 0000-0002-0949-8752 surname: Daly fullname: Daly, M J organization: The Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA – sequence: 46 givenname: I orcidid: 0000-0002-4990-556X surname: Liberzon fullname: Liberzon, I organization: VA Ann Arbor Health System, Ann Arbor, MI, USA – sequence: 47 givenname: K J surname: Ressler fullname: Ressler, K J organization: Department of Psychiatry, McLean Hospital, Belmont, MA, USA – sequence: 48 givenname: C M surname: Nievergelt fullname: Nievergelt, C M organization: Department of Psychiatry, University of California, San Diego, San Diego, CA, USA – sequence: 49 givenname: K C surname: Koenen fullname: Koenen, K C organization: Department of Epidemiology, Harvard T. 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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28439101$$D View this record in MEDLINE/PubMed |
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| Title | Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability |
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