Genome-wide association studies in non-anxiety individuals identified novel risk loci for depression. Issue 1 (22nd June 2022)

• Record Type: Journal Article
• Authors: Cheng, Bolun; Qi, Xin; Meng, Peilin; Cheng, Shiqiang; Yang, Xuena; Liu, Li; Yao, Yao; Jia, Yumeng; Wen, Yan; Zhang, Feng
• Is Part Of: European psychiatry. Volume 65:Issue 1(2022)
• Publication Date: 2022-06-22
• Subjects: Depression -- genome-wide association study -- linkage disequilibrium score regression -- non-anxiety; Psychiatry -- Periodicals; Mental illness -- Periodicals; Electronic journals; 616.89
• DOI: 10.1192/j.eurpsy.2022.32
• Languages: English
• ISSNs: 0924-9338

Abstract

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.