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Genomewide association studies of suicide attempts in US soldiers.

Stein MB, Ware EB, Mitchell C, Chen CY, Borja S, Cai T, Dempsey CL, Fullerton CS, Gelernter J, Heeringa SG, Jain S, Kessler RC, Naifeh JA, Nock MK, Ripke S, Sun X, Beckham JC, Kimbrel NA, VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC) Workgroup, Ursano RJ, Smoller JW. Genomewide association studies of suicide attempts in US soldiers. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2017 Dec 1; 174(8):786-797.

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Suicide is a global public health problem with particular resonance for the US military. Genetic risk factors for suicidality are of interest as indicators of susceptibility and potential targets for intervention. We utilized population-based nonclinical cohorts of US military personnel (discovery: N? = 473 cases and N? = 9778 control subjects; replication: N? = 135 cases and N? = 6879 control subjects) and a clinical case-control sample of recent suicide attempters (N? = 51 cases and N? = 112 control subjects) to conduct GWAS of suicide attempts (SA). Genomewide association was evaluated within each ancestral group (European-, African-, Latino-American) and study using logistic regression models. Meta-analysis of the European ancestry discovery samples revealed a genomewide significant locus in association with SA near MRAP2 (melanocortin 2 receptor accessory protein 2) and CEP162 (centrosomal protein 162); 12 genomewide significant SNPs in the region; peak SNP rs12524136-T, OR? = 2.88, p? = 5.24E-10. These findings were not replicated in the European ancestry subsamples of the replication or suicide attempters samples. However, the association of the peak SNP remained significant in a meta-analysis of all studies and ancestral subgroups (OR? = 2.18, 95%CI 1.70, 2.80). Polygenic risk score (PRS) analyses showed some association of SA with bipolar disorder. The association with SNPs encompassing MRAP2, a gene expressed in brain and adrenal cortex and involved in neural control of energy homeostasis, points to this locus as a plausible susceptibility gene for suicidality that should be further studied. Larger sample sizes will be needed to confirm and extend these findings.

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