Transmission distortion of <i>BDNF</i> variants to bipolar disorder type I patients from a south american population isolate^,

Abstract

Recent reports have implicated polymorphisms in the brain derived neurotrophic factor (BDNF) gene region in the etiology of several psychiatric phenotypes, including bipolar disorder. Significant disease association has been reported for the G allele at SNP rs6265, which encodes for Valine at position 66 of BDNF (Val66Met), an apparently functional variant of this key BDNF. Here we examined a sample of 224 bipolar type I patients and available parents (comprising a total of 212 nuclear families) ascertained in a South American population isolate (Antioquia, Colombia). We tested for transmission distortion to bipolar patients of alleles at the rs6265 polymorphism and at a microsatellite marker 1.3 kb away from this SNP. Significant excess transmission of the rs6265 G allele to cases was observed (chi(2) = 10.77, d.f. = 1, P = 0.001). Two-locus haplotype analysis showed a significant global transmission distortion (chi(2) = 16.059, d.f. = 7, P = 0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders.