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.
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Psychological Medicine |
| Vol/bind | 53 |
| Udgave nummer | 7 |
| Sider (fra-til) | 3021-3035 |
| Antal sider | 15 |
| ISSN | 0033-2917 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:This research was specifically funded by the National Institute of Mental Health (NIMH) R01MH073842 and R21MH109917. ZY is funded by NIMH (K01MH109782; R01MH105500; R01MH120170) and a Brain and Behavior Research Foundation NARSAD Young Investigator Award (grant # 28799). KS is supported by NIMH K01MH123914 and L30MH120619. JJC and MM acknowledge grant funding from NIMH (R01MH105500; R01MH110427). CMB acknowledges funding from NIMH (R01MH120170; R01MH124871; R01MH119084; R01MH118278), the Swedish Research Council (VR Dnr: 538-2013-8864), and the Klarman Family Foundation. NM acknowledges grant funding from the Medical Research Council (MR/R004803/1), NIMH (R01MH108595; R21MH115397), the Swiss National Fund (320030_182484), and a Brain and Behavior Research Foundation Independent Investigator Award (grant # 24608 ) . SCZ is supported by NIMH K01MH100435. PGC-ED AN and the AN/OCD transdiagnostis GWAS included controls from the iPSYCH Initiative, funded by the Lundbeck Foundation (grant # R102-A9118 and R155-2014-1724). The UK Medical Research Council and the Wellcome Trust (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and they will serve as guarantors for the contents of this paper. A comprehensive list of grant funding is available on the ALSPAC website.
Funding Information:
We are deeply grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The UK Medical Research Council and the Wellcome Trust (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Dr Micali will serve as guarantor for the contents of this paper. Dr Micali had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding Information:
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.
Publisher Copyright:
© The Author(s), 2022. Published by Cambridge University Press.