Abstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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 (p(replication GWAS1) = 0.02, p(replication GWAS2) = 2.71 × 10(-3)) in CFAP61, and rs11661122 (p(replication GWAS1) = 8.16 × 10(-3), p(replication 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). CONCLUSIONS: Our findings provide novel clues for understanding of the complex genetic architecture of depression.