Predicting eating disorder and anxiety symptoms using disorder-specific and transdiagnostic polygenic scores for anorexia nervosa and obsessive-compulsive disorder

Abstract

Background 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 genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner. Methods Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined N = 3212–5369 per phenotype). Results The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints [β = 0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14; β = 0.05 (s.e. = 0.02) for OCD PGS at age 16] in girls. Conclusions Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific.

The impact of anorexia nervosa and BMI polygenic risk on childhood growth: A 20-year longitudinal population-based study

“…This view is also supported by our previous work and that of others, showing that a PGS for a higher BMI is associated with increased food-approach eating behaviors such as emotional eating as well as disordered eating behaviors such as higher propensity to engage in self-reported binge eating. [44][45][46] Research also indicates that a higher PGS for AN is associated with emotional eating 44 and childhood fussy eating. 47 Taken together, several sources of converging evidence suggest that polygenic risk for AN and/or BMI may impact growth at least in part via eating behaviors.…”

Patterns of Maladaptive Exercise Behavior from ages 14-24 in a Longitudinal Cohort

“…The current study extends a longitudinal investigation of exercise for weight loss and maladaptive exercise in the ALSPAC cohort across a developmental window from adolescence to young adulthood (ages [14][15][16][17][18][19][20][21][22][23][24]. Specifically, we examined the frequency of exercise states, based on the three categories of `No Exercise for Weight Loss', 'Exercise for Weight Loss', and 'Maladaptive Exercise', amongst boys and girls at ages 14, 16, 18, and 24 years old.…”

“…Clarification regarding the prevalence and early predictors of high-risk exercise behavior during adolescence could build knowledge necessary to prevent maladaptive exercise patterns from taking hold. Previous research highlights several potential predictors of maladaptive exercise in young people, including, at a social level: pressures to conform to body image ideals 18 , at a psychological level: weight and shape concerns, negative affect, thinness expectations 6 , and weight-loss motivations for exercise 7 , and, at a biological level: genetic risk for obsessive-compulsive disorder and/or anorexia nervosa 19 .…”

Assessing a multivariate model of brain-mediated genetic influences on disordered eating in the ABCD cohort

“…Depressive symptoms, such as negative affect, often predate the emergence of disordered eating behaviors [35], and generalized anxiety during childhood has been shown to predict ED diagnoses in adolescence [36]. Moreover, premorbid obsessive-compulsive disorder (OCD) symptoms have been reported in AN [37], which may reflect their shared etiology as AN PGS has predicted OCD and anxiety symptoms in girls [38]. As such, efforts to improve risk stratification and early intervention for EDs would benefit from greater knowledge of the neural and behavioral correlates of elevated genetic risk for these illnesses and their related traits.…”