Systematic review of genome-wide association studies of anxiety disorders and neuroticism

Objectives To summarise SNP associations identified by genome-wide association studies (GWASs) of anxiety disorders and neuroticism; to appraise the quality of individual studies, and to assess the ancestral diversity of study participants. Methods We searched PubMed, Scopus, PsychInfo and PubPsych for GWASs of anxiety disorders, non-diagnostic traits (such as anxiety sensitivity), and neuroticism, and extracted all SNPs that surpassed genome-wide significance. We graded study quality using Q-genie scores and reviewed the ancestral diversity of included participants. Results 32 studies met our inclusion criteria. A total of 563 independent significant variants were identified, of which 29 were replicated nominally in independent samples, and 3 were replicated significantly. The studies had good global quality, but many smaller studies were underpowered. Phenotypic heterogeneity for anxiety (and less so for neuroticism) seemed to reflect the complexity of capturing this trait. Ancestral diversity was poor, with 70% of studies including only populations of European ancestry. Conclusion The functionality of genes identified by GWASs of anxiety and neuroticism deserves further investigation. Future GWASs should have larger sample sizes, more rigorous phenotyping and include more ancestrally diverse population groups.