Zeynep Yilmaz1,2,3,4, Katherine Schaumberg2,5, Matthew Halvorsen3, Erica L Goodman6, Leigh C Brosof7, James J Crowley2,3,8, Carol A Mathews9, Manuel Mattheisen8,10,11,12, Gerome Breen13,14, Cynthia M Bulik2,4,15, Nadia Micali16,17,18, Stephanie C Zerwas2. 1. National Centre for Register-based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark. 2. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA. 3. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA. 4. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 5. Department of Psychiatry, University of Wisconsin, Madison, WI, USA. 6. Department of Psychology, University of North Dakota, Grand Forks, ND, USA. 7. Department of Psychological and Brain Sciences, University of Louisville, Louisville, KY, USA. 8. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 9. Department of Psychiatry, Genetics Institute, University of Florida, Gainesville, FL, USA. 10. Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, Aarhus, Denmark. 11. The Lundbeck Foundation Initiative of Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark. 12. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany. 13. Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, King's College London, London, UK. 14. National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust, London, UK. 15. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. 16. Department of Psychiatry, Faculty of Medicine, University of Geneva, HUG, Geneva, Switzerland. 17. Institute of Child Health, University College London, London, UK. 18. Department of Paediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, HUG, Geneva, Switzerland.
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.
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.
Authors: Martin Cederlöf; Laura M Thornton; Jessica Baker; Paul Lichtenstein; Henrik Larsson; Christian Rück; Cynthia M Bulik; David Mataix-Cols Journal: World Psychiatry Date: 2015-10 Impact factor: 49.548
Authors: Lisa Dinkler; Mark J Taylor; Maria Råstam; Nouchine Hadjikhani; Cynthia M Bulik; Paul Lichtenstein; Christopher Gillberg; Sebastian Lundström Journal: Psychol Med Date: 2019-12-17 Impact factor: 7.723
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