Genome-wide analyses of quantitative generalised anxiety symptom severity

Abstract

We performed a genome-wide association meta-analysis of generalised anxiety symptom severity in 693,869 individuals of European ancestry from 14 cohorts. We identified 80 independent genome-wide significant variants within 74 loci, 39 of which were novel for anxiety. SNP-based heritability was 5.9% (SE = 0.15%). Polygenic scores were significantly associated with anxiety symptom severity and disorder in European, African, and South Asian ancestry samples (r2=1.2%-2.9%). Significant genetic correlations were estimated with numerous mental and physical health traits, including case-control anxiety, neuroticism and depression (rg=0.71-0.86), irritable bowel syndrome (rg=0.57), coronary artery disease, endometriosis, and migraine (rg=0.20-0.27). Gene-based and pathway analyses implicated synaptic and axonal processes, with enriched expression in the brain. These findings highlight the additional value of a quantitative approach in anxiety genetics.