Male-specific association of the 2p25 region with suicide attempt in bipolar disorder

Sophia C. Gaynor, Eric T. Monson, Marie E. Gaine, Michael S. Chimenti, Rachel D. Reichman, Meredith Parsons, Lalita Oonthonpan, Peter P. Zandi, James B. Potash, Virginia L. Willour

Research output: Contribution to journalArticle

Abstract

We previously conducted a genome-wide association study (GWAS) of attempted suicide within bipolar disorder, which implicated common variation in the 2p25 region primarily in males. The top association signal from our GWAS occurred in an intergenic region of 2p25 (p = 5.07 × 10−8) and was supported by two independent studies. In the current study, to better characterize the association of the 2p25 region with attempted suicide, we sequenced the entire 350kb 2p25 region in 476 bipolar suicide attempters and 473 bipolar non-attempters using targeted next-generation sequencing. This fine-mapping project identified 4,681 variants in the 2p25 region. We performed both gene-level and individual-variant tests on our sequencing results and identified 375 variants which were nominally significant (p < 0.05) and three common variants that were significantly associated with attempted suicide in males (corrected p = 0.035, odds ratio (OR) = 2.13). These three variants are in strong linkage disequilibrium with the top variant from our GWAS. Our top five variants are also predicted expression quantitative trait loci (eQTL) for three genes in the 2p25 region based on publicly available brain expression databases. Our sequencing and eQTL data implicate these three genes – SH3YL1, ACP1, and FAM150B – and three additional pathways – androgen receptor, Wnt signaling, and glutamatergic/GABAergic signaling – in the association of the 2p25 region with suicide. The current study provides additional support for an association of the 2p25 region with attempted suicide in males and identifies several candidate genes and pathways that warrant further investigation to understand their role in suicidal behavior.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalJournal of Psychiatric Research
Volume121
DOIs
StatePublished - Feb 2020

Fingerprint

Attempted Suicide
Bipolar Disorder
Suicide
Genome-Wide Association Study
Quantitative Trait Loci
Genes
Intergenic DNA
Linkage Disequilibrium
Androgen Receptors
Odds Ratio
Databases
Brain

Keywords

  • 2p25
  • Bipolar
  • Genetics
  • Sequencing
  • Sex-specific
  • Suicide

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Gaynor, S. C., Monson, E. T., Gaine, M. E., Chimenti, M. S., Reichman, R. D., Parsons, M., ... Willour, V. L. (2020). Male-specific association of the 2p25 region with suicide attempt in bipolar disorder. Journal of Psychiatric Research, 121, 151-158. https://doi.org/10.1016/j.jpsychires.2019.11.009

Male-specific association of the 2p25 region with suicide attempt in bipolar disorder. / Gaynor, Sophia C.; Monson, Eric T.; Gaine, Marie E.; Chimenti, Michael S.; Reichman, Rachel D.; Parsons, Meredith; Oonthonpan, Lalita; Zandi, Peter P.; Potash, James B.; Willour, Virginia L.

In: Journal of Psychiatric Research, Vol. 121, 02.2020, p. 151-158.

Research output: Contribution to journalArticle

Gaynor, SC, Monson, ET, Gaine, ME, Chimenti, MS, Reichman, RD, Parsons, M, Oonthonpan, L, Zandi, PP, Potash, JB & Willour, VL 2020, 'Male-specific association of the 2p25 region with suicide attempt in bipolar disorder', Journal of Psychiatric Research, vol. 121, pp. 151-158. https://doi.org/10.1016/j.jpsychires.2019.11.009
Gaynor, Sophia C. ; Monson, Eric T. ; Gaine, Marie E. ; Chimenti, Michael S. ; Reichman, Rachel D. ; Parsons, Meredith ; Oonthonpan, Lalita ; Zandi, Peter P. ; Potash, James B. ; Willour, Virginia L. / Male-specific association of the 2p25 region with suicide attempt in bipolar disorder. In: Journal of Psychiatric Research. 2020 ; Vol. 121. pp. 151-158.
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AU - Reichman, Rachel D.

AU - Parsons, Meredith

AU - Oonthonpan, Lalita

AU - Zandi, Peter P.

AU - Potash, James B.

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