Abstract
Objectives To assess bidirectional effects of anxiety and anorexia nervosa (AN) phenotypes. Design Two-sample Mendelian randomization.
Setting Genome-wide association study (GWAS) summary statistics from the Psychiatric Genomics Consortium (PGC), analysis of the UK Biobank sample, and Anxiety Neuro Genetics Study (ANGST) consortium.
Participants European descent participants from the PGC (n = 14,477), UK Biobank (n = 348,219), and ANGST consortium (n = 17,310, and n = 18,186).
Main outcome measures AN diagnosis, worry, anxiety disorder pathology (case-control and quantitative phenotypes).
Results We found evidence of a moderate genetic correlation between worry and AN (Rg = 0.36, SE = 0.05, p < 0.001), and the Mendelian randomization analysis supported a causal influence of worry on AN (OR = 2.14, 95% CI: 1.18 to 3.90, p = 0.01). There was no clear evidence for a causal effect of AN on worry in this study (B = −0.01, 95% CI: −0.03 to 0.02, p = 0.55). There was no robust evidence for a causal influence of anxiety disorders on AN (for case-control anxiety disorder phenotype: OR = 1.02, 95% CI: 0.69, 1.50, p = 0.922; for quantitative anxiety disorder phenotype: OR = 4.26, 95% CI: 0.49, 36.69, p = 0.187). There was no robust evidence for a causal effect of AN on anxiety disorders (for case control anxiety disorder phenotype: OR = 1.00, 95% CI: 0.72, 1.38, p = 0.981; for quantitative anxiety disorder phenotype: B = 0.01, 95% CI: −0.06, 0.6=09, p = 0,761). AN and anxiety disorder phenotypes were not genetically correlated (for case-control anxiety disorder phenotype: Rg = 0.10, se = 0.17, p = .56; for quantitative anxiety disorder phenotype: Rg = 0.12, SE = 0.17, p = 0.47).
Conclusions Findings support a role for worry in AN development, highlighting a potential target of future AN prevention efforts. Mechanisms underlying the association should be a focus of future investigation. The relatively small sample sizes of anxiety disorder and AN GWASs may have limited power to detect causal effects; these associations should be studied further.