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.
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 among women 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.
Maher
Brion S
BS
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
Hughes
Hugh B
HB
Zubenko
Wendy N
WN
Zubenko
George S
GS
D017668:Age of Onset; D002889:Chromosomes, Human, Pair 2; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D012008:Recurrence; D012737:Sex Factors
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein