Identification of novel genomic loci for anxiety symptoms and extensive genetic overlap with psychiatric disorders.

Objective: Anxiety disorders are prevalent and anxiety symptoms (ANX) co-occur with many psychiatric disorders. We aimed to identify genomic loci associated with ANX, characterize its genetic architecture, and genetic overlap with psychiatric disorders.

Methods: We included a genome-wide association study of ANX (meta-analysis of UK Biobank and Million Veterans Program, n = 301,732), schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), and validated the findings in the Norwegian Mother, Father, and Child Cohort (n = 95,841). We employed the bivariate causal mixture model and local analysis of covariant association to characterize the genetic architecture including overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of loci associated with anxiety and shared with psychiatric disorders.

Results: Anxiety was polygenic with 12.9k genetic variants and overlapped extensively with psychiatric disorders (4.1k-11.4k variants) with predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 119 novel loci for anxiety by conditioning on the psychiatric disorders, and loci shared between anxiety and MD