Genetic linkage of region containing the CREB1 gene to depressive disorders in families with recurrent, early-onset, major depression: A re-analysis and confirmation of sex-specific effect

Brion S. Maher, Hugh B. Hughes, Wendy N. Zubenko, George S. Zubenko

Research output: Contribution to journalArticle

Abstract

A previously published model-free linkage analysis of chromosome 2q33-35, highlighted by previous case-control studies and supported by within-family analyses employing the transmission disequilibrium test, revealed evidence of sex-specific linkage of the CREB1-containing region of 2q to unipolar mood disorders amongwomen in 81 recurrent, early-onset, major depressive disorder (RE-MDD) families. Since it has been reported that the LODPAL program from S.A.G.E. v.4.0 used to conduct this previous linkage analysis suffers from an increased type I error rate that is exacerbated by covariates such as sex, we re-analyzed the evidence for this sex-specific linkage result using a simulation approach to estimate the empirical significance of our previous results. The results continue to support sex-specific linkage of the CREB1 region to mood disorders among women from families with RE-MDD. Moreover, these results have been supported by a host of additional published findings that implicate sequence variations in CREB1 in the sex-dependent development of syndromic mood disorders, as well as related clinical features and disorders.

Original languageEnglish (US)
Pages (from-to)10-16
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • CREB1
  • Chromosome 2q
  • Genetics
  • Major depression
  • Sex specificity
  • Unipolar mood disorders
  • Women's health

ASJC Scopus subject areas

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

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