Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1

Abstract

The major mood disorders, which include bipolar disorder and major depressive disorder (MDD), are considered heritable traits, although previous genetic association studies have had limited success in robustly identifying risk loci. We performed a meta-analysis of five case-control cohorts for major mood disorder, including over 13,600 individuals genotyped on high-density SNP arrays. We identified SNPs at 3p21.1 associated with major mood disorders (rs2251219, P = 3.63 x 10(-8); odds ratio = 0.87; 95% confidence interval, 0.83-0.92), with supportive evidence for association observed in two out of three independent replication cohorts. These results provide an example of a shared genetic susceptibility locus for bipolar disorder and MDD.

Figure 1

a. Manhattan plot of the meta-analysis results, generated by Haploview 4.0. Physical position is shown along the x-axis, -log (meta-p-value) is shown along the y-axis, and each chromosome is shown in a distinct color. The red guideline indicates the threshold of genome-wide significance (7.2 ×10⁻⁸). b. Detail of the associated region, generated by SNAP 2.0. Physical position and gene annotations (HapMap release 22) are shown along the x-axis, -log (meta-p-value) is shown on the left y-axis, recombination rate (CEU) on the right y-axis. c. Linkage disequilibrium (r²) as estimated from HapMap 3 phased genotypes, generated by UCSC Genome Browser. Darker red indicates higher values.