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Genomewide association studies of suicide attempts in US soldiers.

Publication ,  Journal Article
Stein, MB; Ware, EB; Mitchell, C; Chen, C-Y; Borja, S; Cai, T; Dempsey, CL; Fullerton, CS; Gelernter, J; Heeringa, SG; Jain, S; Kessler, RC ...
Published in: Am J Med Genet B Neuropsychiatr Genet
December 2017

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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Published In

Am J Med Genet B Neuropsychiatr Genet

DOI

EISSN

1552-485X

Publication Date

December 2017

Volume

174

Issue

8

Start / End Page

786 / 797

Location

United States

Related Subject Headings

  • Young Adult
  • United States
  • Suicide, Attempted
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Military Personnel
  • Male
  • Incidence
  • Humans
  • Genotype
 

Citation

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Chicago
ICMJE
MLA
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Stein, M. B., Ware, E. B., Mitchell, C., Chen, C.-Y., Borja, S., Cai, T., … Smoller, J. W. (2017). Genomewide association studies of suicide attempts in US soldiers. Am J Med Genet B Neuropsychiatr Genet, 174(8), 786–797. https://doi.org/10.1002/ajmg.b.32594
Stein, Murray B., Erin B. Ware, Colter Mitchell, Chia-Yen Chen, Susan Borja, Tianxi Cai, Catherine L. Dempsey, et al. “Genomewide association studies of suicide attempts in US soldiers.Am J Med Genet B Neuropsychiatr Genet 174, no. 8 (December 2017): 786–97. https://doi.org/10.1002/ajmg.b.32594.
Stein MB, Ware EB, Mitchell C, Chen C-Y, Borja S, Cai T, et al. Genomewide association studies of suicide attempts in US soldiers. Am J Med Genet B Neuropsychiatr Genet. 2017 Dec;174(8):786–97.
Stein, Murray B., et al. “Genomewide association studies of suicide attempts in US soldiers.Am J Med Genet B Neuropsychiatr Genet, vol. 174, no. 8, Dec. 2017, pp. 786–97. Pubmed, doi:10.1002/ajmg.b.32594.
Stein MB, Ware EB, Mitchell C, Chen C-Y, 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. Am J Med Genet B Neuropsychiatr Genet. 2017 Dec;174(8):786–797.
Journal cover image

Published In

Am J Med Genet B Neuropsychiatr Genet

DOI

EISSN

1552-485X

Publication Date

December 2017

Volume

174

Issue

8

Start / End Page

786 / 797

Location

United States

Related Subject Headings

  • Young Adult
  • United States
  • Suicide, Attempted
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Military Personnel
  • Male
  • Incidence
  • Humans
  • Genotype