Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

Abstract

Background: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa.

Methods: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472).

Results: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes.

Conclusions: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.

Keywords: ADHD; Anorexia nervosa; Bulimia nervosa; Eating disorders; Genetic epidemiology; Polygenic risk score.

Figure 1

Odd ratios (ORs) of eating disorders (EDs) in individuals with attention-deficit/hyperactivity disorder (ADHD) and their relatives compared with individuals without ADHD and their relatives. The forest plot shows the ORs of any ED, anorexia nervosa (AN), other EDs (i.e., non-AN EDs) (OED), and bulimia nervosa (BN) in index individuals with ADHD and their relatives compared with index individuals without ADHD and their relatives. In general, greater ORs were found in more closely (genetically and familial environmentally) related relatives, suggesting shared genetic and/or familial environmental liabilities between ADHD and these EDs. In general, the ORs appeared to be higher for OED and BN compared with AN in each type of relative, suggesting stronger associations with ADHD in OED and BN than in AN. Bolded values are significant at p < .0001. CI, confidence interval.

Figure 2

Variance explained (R²) and regression coefficient (β) for the association between attention-deficit/hyperactivity disorder (ADHD) polygenic risk scores (PRSs) and eating disorder (ED) symptoms and the association between anorexia nervosa (AN) PRSs and ADHD symptoms. (A, B) Associations between ADHD PRSs and Eating Disorder Inventory-2 (EDI-2) measures of ED symptoms. Panel (A) shows R², and panel (B) shows β and 95% confidence interval (CI). ADHD PRSs across different p-value thresholds showed consistent results in explaining the variance (A) and consistent regression coefficients (B) in each measure of the ED symptoms. (C, D) Associations between AN PRSs and Autism–Tics, ADHD, and Other Comorbidities inventory (A-TAC) measures for ADHD symptoms. Panel (C) shows R², and panel (D) shows β and 95% CI. Variance explained (C) and regression coefficients (D) were less consistent for the associations between AN PRSs and ADHD. AN PRSs across multiple p-value thresholds were not significantly associated with measures of ADHD symptoms in general, although AN PRSs at p-value thresholds p < .00001, p < .01, and p < .05 showed negative associations with the measure of Inattention (p < .05). ADHD_pT, p-value thresholds for ADHD PRSs; AN_pT, p-value thresholds for AN PRSs. PRSs at threshold p < 1.00 were used for the main analysis. PRSs at other p-value thresholds were used for sensitivity tests. *p ≤ .05 and **p ≤ .01 for the associations between PRSs and the symptom measures.