Association and linkage studies between bipolar affective disorder and thepolymorphic CAG/CTG repeat loci ERDA1, SEF2-1B, MAB21L and KCNN3

Several reports have suggested the presence of anticipation in bipolar affe ctive disorder (BPAD). In addition, independent studies using the RED (repe at expansion detection) have shown association between BPAD and longer CAG/ CTG repeats. Therefore loci with large CAG/CTG repeats are plausible candid ates in the inheritance of BPAD. The present study assesses the length of t he repeats in four loci: the ERDA-1 locus which is known to account for mos t of the long CAG repeats detected by RED, the SEF2-1b locus which is place d in a region where positive linkage results have been reported and the loc i MAB21L and KCNN3 as functional candidate genes. A Brazilian case-control sample with 115 unrelated BPAD patients and 196 healthy control subjects an d 14 multiply affected bipolar families was investigated. With the case-con trol design the distribution of alleles between the two groups did not appr oach statistical significance. The extended transmission disequilibrium tes t (ETDT) performed in our families did not show evidence for linkage disequ ilibrium. Parametric and non-parametric linkage analysis also did not provi de support for linkage between any of the four loci and BPAD. Our data do n ot support the hypothesis that variation at the polymorphic CAG/CTG repeat loci ERDA-1, SEF2-1b, MAB21L or KCNN3 influence susceptibility to BPAD in o ur sample.