TY - JOUR
T1 - Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
AU - Eating Disorders Working Group of the Psychiatric Genomics Consortium
AU - German Borderline Genomics Consortium
AU - MVP Suicide Exemplar Workgroup
AU - VA Million Veteran Program
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU - Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
AU - Mullins, Niamh
AU - Kang, Joo Eun
AU - Campos, Adrian I.
AU - Coleman, Jonathan R.I.
AU - Edwards, Alexis C.
AU - Galfalvy, Hanga
AU - Levey, Daniel F.
AU - Lori, Adriana
AU - Shabalin, Andrey
AU - Starnawska, Anna
AU - Su, Mei Hsin
AU - Watson, Hunna J.
AU - Adams, Mark
AU - Awasthi, Swapnil
AU - Gandal, Michael
AU - Hafferty, Jonathan D.
AU - Hishimoto, Akitoyo
AU - Kim, Minsoo
AU - Okazaki, Satoshi
AU - Otsuka, Ikuo
AU - Ripke, Stephan
AU - Ware, Erin B.
AU - Bergen, Andrew W.
AU - Berrettini, Wade H.
AU - Bohus, Martin
AU - Brandt, Harry
AU - Chang, Xiao
AU - Chen, Wei J.
AU - Chen, Hsi Chung
AU - Crawford, Steven
AU - Crow, Scott
AU - DiBlasi, Emily
AU - Duriez, Philibert
AU - Fernández-Aranda, Fernando
AU - Fichter, Manfred M.
AU - Gallinger, Steven
AU - Glatt, Stephen J.
AU - Gorwood, Philip
AU - Guo, Yiran
AU - Hakonarson, Hakon
AU - Halmi, Katherine A.
AU - Hwu, Hai Gwo
AU - Jain, Sonia
AU - Jamain, Stéphane
AU - Jiménez-Murcia, Susana
AU - Johnson, Craig
AU - Kaplan, Allan S.
AU - Kaye, Walter H.
AU - Keel, Pamela K.
AU - Hottenga, Jouke Jan
N1 - Publisher Copyright:
© 2021 Society of Biological Psychiatry
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Background: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
AB - Background: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
KW - Genetic correlation
KW - Genome-wide association study
KW - Pleiotropy
KW - Polygenicity
KW - Suicide
KW - Suicide attempt
UR - https://www.scopus.com/pages/publications/85119273569
U2 - 10.1016/j.biopsych.2021.05.029
DO - 10.1016/j.biopsych.2021.05.029
M3 - Article
C2 - 34861974
AN - SCOPUS:85119273569
SN - 0006-3223
VL - 91
SP - 313
EP - 327
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 3
ER -