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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Zeynep Yilmaz
  • Katherine Schaumberg, University of North Carolina, University of Wisconsin-Madison
  • ,
  • Matthew Halvorsen, University of North Carolina
  • ,
  • Erica L Goodman, University of North Dakota
  • ,
  • Leigh C Brosof, University of Louisville
  • ,
  • James J Crowley, University of North Carolina, Karolinska Institutet
  • ,
  • Carol A Mathews, University of Florida
  • ,
  • Manuel Mattheisen, Karolinska Institutet, Lundbeck Foundation Initiative of Integrative Psychiatric Research (iPSYCH), University of Würzburg
  • ,
  • Gerome Breen, King's College London
  • ,
  • Cynthia M Bulik, University of North Carolina, Karolinska Institutet
  • ,
  • Nadia Micali, University of Geneva, University College London
  • ,
  • Stephanie C Zerwas, University of North Carolina
  • ,
  • Anorexia Nervosa Genetics Initiative

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.

Original languageEnglish
JournalPsychological Medicine
Pages (from-to)1-15
Number of pages15
Publication statusPublished - May 2023

    Research areas

  • Eating disorders, anxiety, developmental cohort, obsesive-compulsive disorder, polygenic scores

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