Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

L. E. Duncan; A. Ratanatharathorn; A. E. Aiello; L. M. Almli; A. B. Amstadter; A. E. Ashley-Koch; D. G. Baker; J. C. Beckham; L. J. Bierut; J. Bisson; B. Bradley; C. Y. Chen; S. Dalvie; L. A. Farrer; S. Galea; M. E. Garrett; J. E. Gelernter; G. Guffanti; M. A. Hauser; E. O. Johnson; R. C. Kessler; N. A. Kimbrel; A. King; N. Koen; H. R. Kranzler; M. W. Logue; A. X. Maihofer; A. R. Martin; M. W. Miller; R. A. Morey; N. R. Nugent; J. P. Rice; S. Ripke; A. L. Roberts; N. L. Saccone; J. W. Smoller; D. J. Stein; M. B. Stein; J. A. Sumner; M. Uddin; R. J. Ursano; D. E. Wildman; R. Yehuda; H. Zhao; M. J. Daly; I. Liberzon; K. J. Ressler; C. M. Nievergelt; K. C. Koenen

doi:10.1038/mp.2017.77

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

L. E. Duncan, A. Ratanatharathorn, A. E. Aiello, L. M. Almli, A. B. Amstadter, A. E. Ashley-Koch, D. G. Baker, J. C. Beckham, L. J. Bierut, J. Bisson, B. Bradley, C. Y. Chen, S. Dalvie, L. A. Farrer, S. Galea, M. E. Garrett, J. E. Gelernter, G. Guffanti, M. A. Hauser, E. O. JohnsonR. C. Kessler, N. A. Kimbrel, A. King, N. Koen, H. R. Kranzler, M. W. Logue, A. X. Maihofer, A. R. Martin, M. W. Miller, R. A. Morey, N. R. Nugent, J. P. Rice, S. Ripke, A. L. Roberts, N. L. Saccone, J. W. Smoller, D. J. Stein, M. B. Stein, J. A. Sumner, M. Uddin, R. J. Ursano, D. E. Wildman, R. Yehuda, H. Zhao, M. J. Daly, I. Liberzon, K. J. Ressler, C. M. Nievergelt, K. C. Koenen

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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 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.

Original language	English
Pages (from-to)	666-673
Number of pages	8
Journal	Molecular Psychiatry
Volume	23
Issue number	3
DOIs	https://doi.org/10.1038/mp.2017.77
State	Published - Mar 1 2018

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Duncan, L. E., Ratanatharathorn, A., Aiello, A. E., Almli, L. M., Amstadter, A. B., Ashley-Koch, A. E., Baker, D. G., Beckham, J. C., Bierut, L. J., Bisson, J., Bradley, B., Chen, C. Y., Dalvie, S., Farrer, L. A., Galea, S., Garrett, M. E., Gelernter, J. E., Guffanti, G., Hauser, M. A., ... Koenen, K. C. (2018). Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability. Molecular Psychiatry, 23(3), 666-673. https://doi.org/10.1038/mp.2017.77

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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 = "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",

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Duncan, LE, Ratanatharathorn, A, Aiello, AE, Almli, LM, Amstadter, AB, Ashley-Koch, AE, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Bradley, B, Chen, CY, Dalvie, S, Farrer, LA, Galea, S, Garrett, ME, Gelernter, JE, Guffanti, G, Hauser, MA, Johnson, EO, Kessler, RC, Kimbrel, NA, King, A, Koen, N, Kranzler, HR, Logue, MW, Maihofer, AX, Martin, AR, Miller, MW, Morey, RA, Nugent, NR, Rice, JP, Ripke, S, Roberts, AL, Saccone, NL, Smoller, JW, Stein, DJ, Stein, MB, Sumner, JA, Uddin, M, Ursano, RJ, Wildman, DE, Yehuda, R, Zhao, H, Daly, MJ, Liberzon, I, Ressler, KJ, Nievergelt, CM & Koenen, KC 2018, 'Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability', Molecular Psychiatry, vol. 23, no. 3, pp. 666-673. https://doi.org/10.1038/mp.2017.77

TY - JOUR

T1 - Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

AU - Duncan, L. E.

AU - Ratanatharathorn, A.

AU - Aiello, A. E.

AU - Almli, L. M.

AU - Amstadter, A. B.

AU - Ashley-Koch, A. E.

AU - Baker, D. G.

AU - Beckham, J. C.

AU - Bierut, L. J.

AU - Bisson, J.

AU - Bradley, B.

AU - Chen, C. Y.

AU - Dalvie, S.

AU - Farrer, L. A.

AU - Galea, S.

AU - Garrett, M. E.

AU - Gelernter, J. E.

AU - Guffanti, G.

AU - Hauser, M. A.

AU - Johnson, E. O.

AU - Kessler, R. C.

AU - Kimbrel, N. A.

AU - King, A.

AU - Koen, N.

AU - Kranzler, H. R.

AU - Logue, M. W.

AU - Maihofer, A. X.

AU - Martin, A. R.

AU - Miller, M. W.

AU - Morey, R. A.

AU - Nugent, N. R.

AU - Rice, J. P.

AU - Ripke, S.

AU - Roberts, A. L.

AU - Saccone, N. L.

AU - Smoller, J. W.

AU - Stein, D. J.

AU - Stein, M. B.

AU - Sumner, J. A.

AU - Uddin, M.

AU - Ursano, R. J.

AU - Wildman, D. E.

AU - Yehuda, R.

AU - Zhao, H.

AU - Daly, M. J.

AU - Liberzon, I.

AU - Ressler, K. J.

AU - Nievergelt, C. M.

AU - Koenen, K. C.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

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U2 - 10.1038/mp.2017.77

DO - 10.1038/mp.2017.77

M3 - Article

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AN - SCOPUS:85032568947

SN - 1359-4184

VL - 23

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EP - 673

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 3

ER -

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

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