MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Zubenko, 2003 PubMed
Full Info	Zubenko, G.S., Maher, B., Hughes, H.B., 3rd, Zubenko, W.N., Stiffler, J.S., Kaplan, B.B. and Marazita, M.L. (2003) Genome-wide linkage survey for genetic loci that influence the development of depressive disorders in families with recurrent, early-onset, major depression. Am J Med Genet B Neuropsychiatr Genet, 123B, 1-18.

Study

Hypothesis or Background
Sample Information	81 families identified by individuals with Recurrent, Early-Onset, Major Depressive Disorder (RE-MDD)
Method Detail	genome-wide linkage analysis
Method Keywords	linkage analysis
Result	The highest maximum LOD score observed, 8.19 (genome-wide adjusted P << 0.0001), occurred for Recurrent Major Depressive Disorder (R-MDD) at D2S2321 (205 cM), located 121 kb proximal to CREB1. Nineteen chromosomal regions contained linkage peaks that reached genome-wide statistical significance (genome-wide adjusted P < 0.05) and ten of these were "highly significant" (adjusted P < 0.001). Six of the 19 linkage peaks were revealed only when the analysis included covariates to control for the effects of sex and linkage to CREB1. Sex-specific susceptibility loci were common and preferentially affected the vulnerability of women to developing unipolar Mood Disorders. Five loci revealed evidence of interaction with the CREB1 locus in determining susceptibility (epistasis). A systematic candidate gene analysis is presented and potential overlaps of the linkage regions for unipolar Mood Disorders with those reported for other psychiatric disorders are discussed.
Conclusions	The findings suggest that genes whose products participate in cellular signaling pathways that converge on CREB, as well as the target genes whose expression they regulate, may also harbor alleles that affect the development of Mood Disorders and related conditions.

Relationships reported by Zubenko, 2003