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

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2010-01, Vol.153B (1), p.10-16
• Main Authors: Maher, Brion S., Hughes III, Hugh B., Zubenko, Wendy N., Zubenko, George S.
• Format: Article
• Language: English
• Subjects: Age of Onset; chromosome 2q; Chromosomes, Human, Pair 2; CREB1; Cyclic AMP Response Element-Binding Protein - genetics; Depression - genetics; Female; Genetic Linkage; genetics; Humans; major depression; Male; Recurrence; Sex Factors; sex specificity; unipolar mood disorders; women's health
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30987

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. © 2009 Wiley‐Liss, Inc.