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GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores

. 2019 Aug 01 ; 176 (8) : 651-660. [epub] 20190605

Language English Country United States Media print-electronic

Document type Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't

Grant support
MC_PC_17228 Medical Research Council - United Kingdom
Z01 MH002810 Intramural NIH HHS - United States
R01 MH104964 NIMH NIH HHS - United States
R01 MH059567 NIMH NIH HHS - United States
R01 MH059545 NIMH NIH HHS - United States
MR/L010305/1 Medical Research Council - United Kingdom
U01 MH079469 NIMH NIH HHS - United States
G1000708 Medical Research Council - United Kingdom
G0800509 Medical Research Council - United Kingdom
R01 MH085548 NIMH NIH HHS - United States
R01 MH123451 NIMH NIH HHS - United States
U01 MH109532 NIMH NIH HHS - United States
R01 MH059566 NIMH NIH HHS - United States
R01 MH059553 NIMH NIH HHS - United States
U01 MH109528 NIMH NIH HHS - United States
R01 MH061675 NIMH NIH HHS - United States
R01 MH059556 NIMH NIH HHS - United States
U01 MH046276 NIMH NIH HHS - United States
R01 MH059535 NIMH NIH HHS - United States
R01 MH059548 NIMH NIH HHS - United States
R01 MH067257 NIMH NIH HHS - United States
R01 MH060870 NIMH NIH HHS - United States
R01 MH081800 NIMH NIH HHS - United States
R01 MH059534 NIMH NIH HHS - United States
R01 MH059571 NIMH NIH HHS - United States
R01 MH059565 NIMH NIH HHS - United States
U01 MH109536 NIMH NIH HHS - United States
U01 MH079470 NIMH NIH HHS - United States
R01 MH059587 NIMH NIH HHS - United States
R01 MH059533 NIMH NIH HHS - United States
U01 MH109514 NIMH NIH HHS - United States
R00 MH101367 NIMH NIH HHS - United States
R01 MH059586 NIMH NIH HHS - United States
R01 MH059588 NIMH NIH HHS - United States
U01 MH046318 NIMH NIH HHS - United States
R01 MH119243 NIMH NIH HHS - United States
R01 MH060879 NIMH NIH HHS - United States
MC_QA137853 Medical Research Council - United Kingdom
R01 MH060068 NIMH NIH HHS - United States

OBJECTIVE: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium. METHODS: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders. RESULTS: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%). CONCLUSIONS: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

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