Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

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.Peer reviewe

AHC interview with Marianne Ehrlich Ross.

00:00 short description of life story1:50 family background5:35 life in Vienna and awareness of situation in Germany8:00 emigration8:30 religious traditions of family11:10 going back to Vienna13:55 emigration17:55 living in England24:55 antisemitism in Europe26:05 being refugees in England28:05 coming to the US33:45 Israel and Zionism37:20 connections to Austria today38:15 children39:45 speaking German40:30 identity today41:50 opinions on Austria and Europe49:15 final statementMarch 17, 2017Marianne Ehrlich Ross was born on July 8, 1934 in Vienna, Austria, where she grew up in the 2nd District. Because her father had Czech citizenship, her family first fled to Prague, and then they then emigrated to England, where they spent the war years. In 1948 Marianne came to the United States.Austrian Heritage Collectio