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Uncommon Protein-Coding Variants Associated With Suicide Attempt in a Diverse Sample of U.S. Army Soldiers.
Wilkerson, Matthew D; Hupalo, Daniel; Gray, Joshua C; Zhang, Xijun; Wang, Jiawei; Girgenti, Matthew J; Alba, Camille; Sukumar, Gauthaman; Lott, Nathaniel M; Naifeh, James A; Aliaga, Pablo; Kessler, Ronald C; Turner, Clesson; Pollard, Harvey B; Dalgard, Clifton L; Ursano, Robert J; Stein, Murray B.
Afiliación
  • Wilkerson MD; Center for Military Precision Health, Uniformed Services University, Bethesda, Maryland; Department of Anatomy, Physiology, and Genetics, Uniformed Services University, Bethesda, Maryland.
  • Hupalo D; Center for Military Precision Health, Uniformed Services University, Bethesda, Maryland.
  • Gray JC; Department of Medical and Clinical Psychology, Uniformed Services University, Bethesda, Maryland.
  • Zhang X; Center for Military Precision Health, Uniformed Services University, Bethesda, Maryland.
  • Wang J; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
  • Girgenti MJ; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
  • Alba C; Center for Military Precision Health, Uniformed Services University, Bethesda, Maryland.
  • Sukumar G; Center for Military Precision Health, Uniformed Services University, Bethesda, Maryland.
  • Lott NM; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland.
  • Naifeh JA; Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University, Bethesda, Maryland.
  • Aliaga P; Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University, Bethesda, Maryland.
  • Kessler RC; Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.
  • Turner C; Department of Pediatrics, Uniformed Services University, Bethesda, Maryland.
  • Pollard HB; Department of Anatomy, Physiology, and Genetics, Uniformed Services University, Bethesda, Maryland.
  • Dalgard CL; Center for Military Precision Health, Uniformed Services University, Bethesda, Maryland; Department of Anatomy, Physiology, and Genetics, Uniformed Services University, Bethesda, Maryland.
  • Ursano RJ; Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University, Bethesda, Maryland.
  • Stein MB; Department of Psychiatry, University of California San Diego, La Jolla, California; Herbert Wertheim School of Public Health, University of California San Diego, La Jolla, California; VA San Diego Healthcare System, San Diego, California. Electronic address: mstein@health.ucsd.edu.
Biol Psychiatry ; 96(1): 15-25, 2024 Jul 01.
Article en En | MEDLINE | ID: mdl-38141912
ABSTRACT

BACKGROUND:

Suicide is a societal and public health concern of global scale. Identifying genetic risk factors for suicide attempt can characterize underlying biology and enable early interventions to prevent deaths. Recent studies have described common genetic variants for suicide-related behaviors. Here, we advance this search for genetic risk by analyzing the association between suicide attempt and uncommon variation exome-wide in a large, ancestrally diverse sample.

METHODS:

We sequenced whole genomes of 13,584 soldiers from the Army STARRS (Army Study to Assess Risk and Resilience in Servicemembers), including 979 individuals with a history of suicide attempt. Uncommon, nonsilent protein-coding variants were analyzed exome-wide for association with suicide attempt using gene-collapsed and single-variant analyses.

RESULTS:

We identified 19 genes with variants enriched in individuals with history of suicide attempt, either through gene-collapsed or single-variant analysis (Bonferroni padjusted < .05). These genes were CIB2, MLF1, HERC1, YWHAE, RCN2, VWA5B1, ATAD3A, NACA, EP400, ZNF585A, LYST, RC3H2, PSD3, STARD9, SGMS1, ACTR6, RGS7BP, DIRAS2, and KRTAP10-1. Most genes had variants across multiple genomic ancestry groups. Seventeen of these genes were expressed in healthy brain tissue, with 9 genes expressed at the highest levels in the brain versus other tissues. Brains from individuals deceased from suicide aberrantly expressed RGS7BP (padjusted = .035) in addition to nominally significant genes including YWHAE and ACTR6, all of which have reported associations with other mental disorders.

CONCLUSIONS:

These results advance the molecular characterization of suicide attempt behavior and support the utility of whole-genome sequencing for complementing the findings of genome-wide association studies in suicide research.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Intento de Suicidio / Personal Militar Límite: Adult / Female / Humans / Male País/Región como asunto: America do norte Idioma: En Revista: Biol Psychiatry Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Intento de Suicidio / Personal Militar Límite: Adult / Female / Humans / Male País/Región como asunto: America do norte Idioma: En Revista: Biol Psychiatry Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos