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

The major mood disorders, which include bipolar disorder (BD) and major depressive disorder (MDD), are substantially heritable, but few risk loci have been identified. We performed a meta-analysis of 5 major mood disorder case-control samples, including over 13,600 unique individuals genotyped with approximately 500,000 to 1 million single nucleotide polymorphism (SNP) markers on high-density arrays. Allele-wise association results were meta-analyzed with a method that weights results by sample size. We found genome-wide significant evidence that SNPs in a region of chromosome 3p21.1were associated with major mood disorders. The SNP rs2251219 returned the smallest meta-analysis p-value, 3.63 × 10(−8), with a pooled odds ratio of 0.87. Supportive results were observed in 2 out of 3 independent samples tested in a replication study. These results implicate one or more genes in this region in the etiology of major mood disorders and suggest that BD and MDD share genetic risk factors.