Large epigenome-wide association study identifies multiple novel differentially methylated CpG sites associated with suicidal thoughts and behaviors in veterans

Frontiers in Psychiatry

Psychiatry

Clara Mellows¹  Melanie E. Garrett²  Michael A. Hauser²  Allison E. Ashley-Koch²  Michelle F. Dennis³  Mariah K. Evans³  Lauren P. Hair³  Jean C. Beckham⁴  Nathan A. Kimbrel⁵ 

[1]Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

[2]Duke Molecular Physiology Institute, Durham, NC, United States

[3]Durham Veterans Affairs (VA) Health Care System, Durham, NC, United States

[4]Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States

[5]Durham Veterans Affairs (VA) Health Care System, Durham, NC, United States

[6]VA Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, United States

[7]Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States

[8]Durham Veterans Affairs (VA) Health Care System, Durham, NC, United States

[9]VA Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, United States

[10]VA Health Services Research and Development Center of Innovation to Accelerate Discovery and Practice Transformation, Durham, NC, United States

[11]Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States

关键词: suicide;    epigenetics;    methylation;    psychiatry;    suicidal ideation;   

DOI  :  10.3389/fpsyt.2023.1145375

 received in 2023-01-16, accepted in 2023-04-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe U.S. suicide mortality rate has steadily increased during the past two decades, particularly among military veterans; however, the epigenetic basis of suicidal thoughts and behaviors (STB) remains largely unknown.MethodsTo address this issue, we conducted an epigenome-wide association study of DNA methylation (DNAm) of peripheral blood samples obtained from 2,712 U.S. military veterans.ResultsThree DNAm probes were significantly associated with suicide attempts, surpassing the multiple testing threshold (FDR q-value <0.05), including cg13301722 on chromosome 7, which lies between the genes SLC4A2 and CDK5; cg04724646 in PDE3A; and cg04999352 in RARRES3. cg13301722 was also found to be differentially methylated in the cerebral cortex of suicide decedents in a publicly-available dataset (p = 0.03). Trait enrichment analysis revealed that the CpG sites most strongly associated with STB in the present sample were also associated with smoking, alcohol consumption, maternal smoking, and maternal alcohol consumption, whereas pathway enrichment analysis revealed significant associations with circadian rhythm, adherens junction, insulin secretion, and RAP-1 signaling, each of which was recently associated with suicide attempts in a large, independent genome-wide association study of suicide attempts of veterans.DiscussionTaken together, the present findings suggest that SLC4A2, CDK5, PDE3A, and RARRES3 may play a role in STB. CDK5, a member of the cyclin-dependent kinase family that is highly expressed in the brain and essential for learning and memory, appears to be a particularly promising candidate worthy of future study; however, additional work is still needed to replicate these finding in independent samples.

【 授权许可】

Unknown   
Copyright © 2023 Kimbrel, Garrett, Evans, Mellows, Dennis, Hair, Hauser, the VA Mid-Atlantic MIRECC Workgroup, Ashley-Koch and Beckham.