Abstract

Major depressive disorder (MDD) and substance use disorders (SUD) are complex behavioral disorders with 40-50% heritability. Recently, Zubenko and colleagues reported that the 124 bp allele of D2S2944, a tetranucleotide repeat marker on 2q35, is strongly associated with recurrent, early onset MDD (RE-MDD) and alcohol use disorders in women. To test this hypothesis, we examined the association of the 124 bp allele in a subset of 171 adoptees from the Iowa Adoption Studies, a population with high rates of MDD and SUD. We report that in our population, the 124 bp allele significantly associated with RE-MDD in women. There was slight evidence of an increased of SUD in women with the 124 bp allele with the rate of cannabis use disorders reaching statistical significance (P < 0.04) before correction for multiple comparisons. Given the history of prior studies implicating 2q35 as a locus encoding vulnerability to co-morbid alcoholism and depression, these findings strongly suggest that sequence variation conveying increased susceptibility to MDD and possibly SUD is in close proximity to D2S2944.

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