Association study of serotonin pathway genes in attempted suicide

Jennifer T. Judy, Fayaz Seifuddin, Pamela B. Mahon, Yuqing Huo, Fernando S. Goes, Dubravka Jancic, Barbara Schweizer, Francis M. Mondimore, Dean F. Mackinnon, J. Raymond Depaulo, Elliot S. Gershon, Francis J. Mcmahon, David J. Cutler, Peter P. Zandi, James B. Potash, Virginia L. Willour

Research output: Contribution to journalArticle

Abstract

Epidemiological studies, such as family, twin, and adoption studies, demonstrate the presence of a heritable component to both attempted and completed suicide. Some of this heritability is accounted for by the presence of comorbid psychiatric disorders, but the evidence also indicates that a portion of this heritability is specific to suicidality. The serotonergic system has been studied extensively in this phenotype, but findings have been inconsistent, possibly due to the presence of multiple susceptibility variants and/or gene-gene interactions. In this study, we genotyped 174 tag and coding single nucleotide polymorphisms (SNPs) from 17 genes within the serotonin pathway on 516 subjects with a major mood disorder and a history of a suicide attempt (cases) and 515 healthy controls, with the goal of capturing the common genetic variation across each of these candidate genes. We tested the 174 markers in single-SNP, haplotype, gene-based, and epistasis analyses. While these association analyses identified multiple marginally significant SNPs, haplotypes, genes, and interactions, none of them survived correction for multiple testing. Additional studies, including assessment in larger sample sets and deep resequencing to identify rare causal variants, may be required to fully understand the role that the serotonin pathway plays in suicidal behavior.

Original languageEnglish (US)
Pages (from-to)112-119
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume159 B
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Bipolar disorder
  • Major depression
  • Suicidal behavior

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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