Genome-wide scan of bipolar disorder and investigation of population stratification effects on linkage: Support for susceptibility loci at 4q21, 7q36, 9p21, 12q24, 14q24, and 16p13

Bipolar disorder (BPD) is a complex genetic disorder with cycling symptoms of depression and mania. Despite the extreme complexity of this psychiatric disorder, attempts to localize genes which confer vulnerability to the disorder have had some success. Chromosomal regions including 4p16,12q24,18p11, 18q22, and 21q21 have been repeatedly linked to BPD in different populations. Here we present the results of a whole genome scan for linkage to BPD in an Irish population. Our most significant result was at 14q24 which yielded a non-parametric LOD (NPL) score of 3.27 at the D14S588 marker with a nominal P-value of 0.0006 under a narrow (bipolar type I only) model of affection. We previously reported linkage to 14q22-24 in a subset of the families tested in this analysis. We also obtained suggestive evidence for linkage at 4q21, 9p21, 12q24, and 16p13, chromosomal regions that have all been previously linked to BPD. Additionally, we report on a novel approach to linkage analysis, STRUCTURE-Guided Linkage Analysis (SGLA), which is designed to reduce genetic heterogeneity and increase the power to detect linkage. Application of this technique resulted in more highly significant evidence for linkage of BPD to three regions including 16p13, a locus that has been repeatedly linked to numerous psychiatric disorders. (c) 2007 Wiley-Liss, Inc.