Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Dec;174(8):786-797.
doi: 10.1002/ajmg.b.32594. Epub 2017 Sep 13.

Genomewide association studies of suicide attempts in US soldiers

Murray B Stein  1   2 , Erin B Ware  3 , Colter Mitchell  3 , Chia-Yen Chen  4   5   6 , Susan Borja  7 , Tianxi Cai  8 , Catherine L Dempsey  9 , Carol S Fullerton  9 , Joel Gelernter  10 , Steven G Heeringa  3 , Sonia Jain  2 , Ronald C Kessler  11 , James A Naifeh  9 , Matthew K Nock  12 , Stephan Ripke  6 , Xiaoying Sun  2 , Jean C Beckham  13   14 , Nathan A Kimbrel  13   14 ; VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC) Workgroup  14 ; Robert J Ursano  9 , Jordan W Smoller  4   5   6
Affiliations

Genomewide association studies of suicide attempts in US soldiers

Murray B Stein et al. Am J Med Genet B Neuropsychiatr Genet. 2017 Dec.

Abstract

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.

Keywords: genetics; genomewide association; military; risk; suicide; suicide attempt.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Lifetime suicide attempt cases vs. non-suicide attempt controls, NSS(1,2) a) Manhattan plot (left side) and quantile-quantile plot (right side) for genome-wide association study of lifetime suicide attempt, controlling for ten ethnicity-specific principal components in European (EUR) sample b) Manhattan plot (left side) and quantile-quantile plot (right side) for genome-wide association study of lifetime suicide attempt, controlling for ten ethnicity-specific principal components in African (AFR) sample c) Manhattan plot (left side) and quantile-quantile plot (right side) for genome-wide association study of lifetime suicide attempt, controlling for ten ethnicity-specific principal components in Latino (LAT) sample
Figure 1
Figure 1
Lifetime suicide attempt cases vs. non-suicide attempt controls, NSS(1,2) a) Manhattan plot (left side) and quantile-quantile plot (right side) for genome-wide association study of lifetime suicide attempt, controlling for ten ethnicity-specific principal components in European (EUR) sample b) Manhattan plot (left side) and quantile-quantile plot (right side) for genome-wide association study of lifetime suicide attempt, controlling for ten ethnicity-specific principal components in African (AFR) sample c) Manhattan plot (left side) and quantile-quantile plot (right side) for genome-wide association study of lifetime suicide attempt, controlling for ten ethnicity-specific principal components in Latino (LAT) sample
Figure 2
Figure 2
Region around genome-wide significant SNPs from the European ancestry NSS(1,2) discovery meta-analysis, chr6:[84303043−85303043], hg19, a) before adjustment for history of major depressive episode and b) after adjustment for lifetime history of major depressive episode
Figure 3
Figure 3
Forest Plot and Fixed Effects Meta-Analysis for Lifetime Suicide Attempt for Top SNP in MRAP2
See this image and copyright information in PMC

References

    1. Afifi TO, Taillieu T, Zamorski MA, Turner S, Cheung K, Sareen J. Association of Child Abuse Exposure With Suicidal Ideation, Suicide Plans, and Suicide Attempts in Military Personnel and the General Population in Canada. JAMA Psychiatry. 2016;73(3):229–238. - PubMed
    1. Anglemyer A, Miller ML, Buttrey S, Whitaker L. Suicide Rates and Methods in Active Duty Military Personnel, 2005 to 2011: A Cohort Study. Ann Intern Med. 2016;165(3):167–174. - PubMed
    1. Asai M, Ramachandrappa S, Joachim M, Shen Y, Zhang R, Nuthalapati N, Ramanathan V, Strochlic DE, Ferket P, Linhart K, Ho C, Novoselova TV, Garg S, Ridderstrale M, Marcus C, Hirschhorn JN, Keogh JM, O'Rahilly S, Chan LF, Clark AJ, Farooqi IS, Majzoub JA. Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science. 2013;341(6143):275–278. - PMC - PubMed
    1. Ashley-Koch AE, Garrett ME, Gibson J, Liu Y, Dennis MF, Kimbrel NA, Veterans Affairs Mid-Atlantic Mental Illness Research E, Clinical Center W. Beckham JC, Hauser MA. Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. J Affect Disord. 2015;184:225–234. - PMC - PubMed
    1. Center AFHS. Surveillance Snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998–2013. 2014:21. - PubMed