Genome-wide association studies in non-anxiety individuals identified novel risk loci for depression.

Abstract

Depression is a debilitating mental disorder that often coexists with anxiety. The genetic mechanisms of depression and anxiety have considerable overlap, and studying depression in non-anxiety samples could help to discover novel gene. We assess the genetic variation of depression in non-anxiety samples, using genome-wide association studies (GWAS) and linkage disequilibrium score regression (LDSC). The GWAS of depression score and self-reported depression were conducted using the UK Biobank samples, comprising 99,178 non-anxiety participants with anxiety score <5 and 86,503 non-anxiety participants without self-reported anxiety, respectively. Replication analysis was then performed using two large-scale GWAS summary data of depression from Psychiatric Genomics Consortium (PGC). LDSC was finally used to evaluate genetic correlations with 855 health-related traits based on the primary GWAS. Two genome-wide significant loci for non-anxiety depression were identified: rs139702470 (p=1.54×10-8, OR=0.29) locate in PIEZO2, and rs6046722 (p=2.52×10-8, OR=1.09) locate in CFAP61. These associated genes were replicated in two GWAS of depression from PGC, such as rs1040582 (preplication GWAS1=0.02, preplication GWAS2=2.71×10-3) in CFAP61, and rs11661122 (preplication GWAS1=8.16×10-3, preplication GWAS2=8.08×10-3) in PIEZO2. LDSC identified 19 traits genetically associated with non-anxiety depression (p<0.001), such as marital separation/divorce (rg=0.45, SE=0.15). Our findings provide novel clues for understanding of the complex genetic architecture of depression.