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

doi:10.1016/j.jpsychires.2019.11.009

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

Journal article

Peer reviewed

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 and Virginia L Willour

Journal of psychiatric research, Vol.121, pp.151-158

02/2020

DOI: 10.1016/j.jpsychires.2019.11.009

PMID: 31830721

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https://www.ncbi.nlm.nih.gov/pmc/articles/8344384View

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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.

Bipolar

Genetics

2p25

Suicide

Sequencing

Sex-specific

Details

Title: Subtitle: Male-specific association of the 2p25 region with suicide attempt in bipolar disorder
Creators: Sophia C Gaynor - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
Eric T Monson - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
Marie E Gaine - Molecular Physiology and Biophysics, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA
Michael S Chimenti - Bioinformatics Division, Iowa Institute of Human Genetics, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
Rachel D Reichman - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
Meredith Parsons - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
Lalita Oonthonpan - Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
Peter P Zandi - Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA
James B Potash - Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA
Virginia L Willour - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
Resource Type: Journal article
Publication Details: Journal of psychiatric research, Vol.121, pp.151-158
DOI: 10.1016/j.jpsychires.2019.11.009
PMID: 31830721
NLM abbreviation: J Psychiatr Res
ISSN: 0022-3956
eISSN: 1879-1379
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01MH079240; DOI: 10.13039/100008893, name: University of Iowa Medical Scientist Training Program, award: 5 T32 GM007337; DOI: 10.13039/100001455, name: American Foundation for Suicide Prevention, award: PDF-0-067-12
Language: English
Date published: 02/2020
Academic Unit: Psychiatry; Pathology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Biochemistry and Molecular Biology; Iowa Institute of Human Genetics
Record Identifier: 9984065466502771

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