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

Zeynep Yilmaz^{1

2

3

4}, Katherine Schaumberg^{2

5}, Matthew Halvorsen³, Erica L Goodman⁶, Leigh C Brosof⁷, James J Crowley^{2

3

8}; Anorexia Nervosa Genetics Initiative; Eating Disorders Working Group of the Psychiatric Genomics Consortium; Tourette Syndrome/Obsessive-Compulsive Disorder Working Group of the Psychiatric Genomics Consortium; Carol A Mathews⁹, Manuel Mattheisen^{8

10

11

12}, Gerome Breen^{13

14}, Cynthia M Bulik^{2

4

15}, Nadia Micali^{16

17

18}, Stephanie C Zerwas²

Affiliations

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.

PMID: 35243971
PMCID: PMC9440960
DOI: 10.1017/S0033291721005079

Meta-Analysis

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

Zeynep Yilmaz et al. Psychol Med. 2023 May.

. 2023 May;53(7):3021-3035.

doi: 10.1017/S0033291721005079. Epub 2022 Mar 4.

Authors

Affiliations

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.

PMID: 35243971
PMCID: PMC9440960
DOI: 10.1017/S0033291721005079

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.

Keywords: Eating disorders; anxiety; developmental cohort; obsesive-compulsive disorder; polygenic scores.

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Conflict of interest statement

CAM has received funding for a book contract with W.W. Norton, Inc., serves as the co-chair of the Tourette Association of America scientific advisory board, is a member of the International OCD Foundation scientific and clinical advisory board, as well as a member of the steering committee for the Family Foundation for OCD Research. GB received grant funding and consultancy fees in preclinical genetics from Eli Lilly, consultancy fees from Otsuka, and has received honoraria from Illumina. CMB has received grant support and served on Shire Scientific Advisory Board, is a consultant for Idorsia, and receives author royalties from Pearson. All other authors have no conflicts of interest to disclose.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical