Predicting Eating Disorder and Anxiety Symptoms Using Anorexia Nervosa and Obsessive-Compulsive Disorder Polygenic Scores

Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetic factors in the expression of eating disorders and OCD/anxiety phenotypes. We examined whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorders, OCD, and anxiety symptoms in a large population-based developmental cohort. Using summary statistics files from the Psychiatric Genomics Consortium Freeze 2 AN and Freeze 1 OCD GWAS, we first conducted an AN/OCD transdiagnostic GWAS meta-analysis and then calculated PGS for AN, OCD, and AN/OCD in participants from the Avon Longitudinal Study of Parents and Children with available genetic and phenotype data on eating disorder, OCD, and anxiety diagnoses and symptoms (sample size 3,212-5,369 per phenotype). We observed sex differences in the PGS prediction of eating disorder, OCD, and anxiety-related phenotypes, with AN genetic risk manifesting at an earlier age and playing a more prominent role in eating disorder phenotypes in boys than in girls. Compulsive exercise was the only phenotype predicted by all three PGS (e.g., P AN(boys) =0.0141 at age 14; P OCD(girls) =0.0070 at age 16; P AN/OCD(all) =0.0297 at age 14). Our results suggest that earlier detection of eating disorder, OCD, and anxiety-related symptoms could be made possible by including measurement of genetic risk for these psychiatric conditions while being mindful of sex differences.