Genome-wide linkage survey for genetic loci that affect the risk of suicide attempts in families with recurrent, early-onset, major depression

George S. Zubenko, Brion S. Maher, Hugh B. Hughes, Wendy N. Zubenko, J. Scott Stiffler, Mary L. Marazita

Research output: Contribution to journalReview articlepeer-review

Abstract

We previously described the results of a genome-wide linkage survey for genetic loci that influenced the development of unipolar mood disorders in 81 families identified by individuals with Recurrent, Early-Onset, Major Depressive Disorder (RE-MDD) [Zubenko et al. 2003b; Am J Med Genet (Neuropsychiatr Genet) 123B:1-18]. In the current study, we extended this linkage analysis by including the history of a suicide attempt as a covariate to identify chromosomal regions that harbor genes that influence the risk of this behavior in the context of mood disorders. This approach identified six linkage peaks with maximum multipoint ΔLOD scores that reached genome-wide adjusted levels of significance (2p, 5q, 6q, 8p, 11q, and Xq). Four of these (2p, 6q, 8p, and Xq) exceeded the criterion for "highly-significant linkage" (genome-wide adjusted P < 0.001) recommended by Lander and Kruglyak [1995; Nat Genet 11:241-246]. The strongest evidence for linkage was observed in analyses employing affected relative pairs (ARPs) with the most severe and disabling Mood Disorders: Depression Spectrum Disorder and RE-MDD. The highest ΔLOD score that emerged from this linkage analysis, 5.08, occurred for ARPs with Depression Spectrum Disorder at D8S1145 (37.0 cM, 18.2 Mbps,P < 0.0601) at cytogenetic location 8p22-p21. Significant linkage results on Xq arose from analyses of ARPs with RE-MDD at DXS1047 (143 cM, 127.8 Mbps, ΔLOD = 3.87, P < 0.0001), a finding that may contribute to the higher rate of suicide attempts among women than men. These findings provide evidence for suicide risk loci that are independent of susceptibility loci for Mood Disorders, and suggest that the capacity for suicide risk loci to affect the development of suicidal behavior depends on the psychiatric disorder or subtype with which they interact.

Original languageEnglish (US)
Pages (from-to)47-54
Number of pages8
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume129 B
Issue number1
DOIs
StatePublished - Aug 15 2004
Externally publishedYes

Keywords

  • Depression spectrum
  • Genes
  • Major depression
  • Suicide
  • Suicide attempts

ASJC Scopus subject areas

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

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