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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.

BACKGROUND: Alcohol involvement has familial associations with bulimic symptoms (i.e., binge eating, inappropriate compensatory behaviors), with several studies indicating a genetic overlap between the two. It is unclear whether overlapping familial risk with alcohol involvement extends to other eating disorder symptoms. Understanding the genetic overlap between alcohol involvement and other eating disorder symptoms may aid in more targeted interventions for comorbid alcohol use-eating disorder symptoms. Thus, we investigated associations between alcohol involvement and 2 core eating disorder symptoms: drive for thinness and body dissatisfaction in adolescent female and male twins. METHODS: We assessed 3 levels of alcohol involvement: alcohol use in the last month, having ever been intoxicated, and alcohol intoxication frequency via self-report. The Eating Disorder Inventory-II assessed drive for thinness and body dissatisfaction. Sex-specific biometrical twin modeling examined the genetic overlap between alcohol involvement and eating disorder symptoms. RESULTS: Phenotypic associations between alcohol involvement, drive for thinness, and body dissatisfaction were significantly greater in girls compared with boys. A majority of the associations between alcohol involvement, drive for thinness, and body dissatisfaction in girls, but not boys, met our threshold for twin modeling (phenotypic r > 0.20). Moderate genetic correlations were observed between the 3 aspects of alcohol involvement and drive for thinness. Moderate genetic correlations were observed between alcohol use and intoxication frequency and body dissatisfaction. CONCLUSIONS: Together with the literature on alcohol involvement and bulimic symptoms, these findings suggest a generalized association between alcohol involvement and eating disorder symptoms in girls, whereas this association may be symptom specific in boys. Genetic correlations indicate that the amount and direction of this genetic overlap