Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies.

Abstract

We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1,221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1,636 screened controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS datasets: STAR*D, Genetics of Recurrent Early-Onset Depression (GenRED) and the publicly-available Genetic Association Information Network MDD dataset (GAIN-MDD). These datasets, totaling 3,957 cases and 3,428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500K, and Perlegen). For each of 2.4 million HapMap II SNPs, using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in ATP6V1B2 (P = 6.78 × 10−7), SP4 (P = 7.68 × 10−7) and GRM7 (P = 1.11 × 10−6). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N = 2,191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. Based on previous biological evidence, we consider GRM7 a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD.