title: Association study of serotonin pathway genes in attempted suicide.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Judy
authors.forename: Fayaz
authors.initials: F
authors.lastname: Seifuddin
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Mahon
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Goes
authors.forename: Dubravka
authors.initials: D
authors.lastname: Jancic
authors.forename: Barbara
authors.initials: B
authors.lastname: Schweizer
authors.forename: Francis M
authors.initials: FM
authors.lastname: Mondimore
authors.forename: Dean F
authors.initials: DF
authors.lastname: Mackinnon
authors.forename: J Raymond
authors.initials: JR
authors.lastname: Depaulo
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: David J
authors.initials: DJ
authors.lastname: Cutler
authors.forename: Peter P
authors.initials: PP
authors.lastname: Zandi
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Willour
mesh_terms: D056726:Genetic Association Studies; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012701:Serotonin / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D013406:Suicide, Attempted / Q000523:psychology; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D012701:Serotonin