Persistent thinness and anorexia nervosa differ on a genomic level
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Thinness and anorexia nervosa are both characterised by persistent low weight. Individuals with anorexia nervosa concurrently report distorted perceptions of their body and engage in weight-loss behaviours, whereas individuals with thinness often wish to gain weight. Both conditions are heritable and share genomics with BMI, but are not genetically correlated with each other. Based on their pattern of genetic associations with other traits, we explored differences between thinness and anorexia nervosa on a genomic level. In Part 1, using publicly available data, we compared genetic correlations of persistent thinness/anorexia nervosa with eleven psychiatric disorders. In Part 2, we identified individuals with adolescent persistent thinness in the Avon Longitudinal Study of Parents and Children (ALSPAC) by latent class growth analysis of measured BMI from 10 to 24 years (n = 6594) and evaluated associations with psychiatric and anthropometric polygenic scores. In Part 1, in contrast to the positive genetic correlations of anorexia nervosa with various psychiatric disorders, persistent thinness showed negative genetic correlations with attention deficit hyperactivity disorder (r gAN = 0.08 vs. r gPT = −0.30), alcohol dependence (r gAN = 0.07 vs. r gPT = −0.44), major depressive disorder (rgAN = 0.27 vs. rgPT = −0.18) and post-traumatic stress disorder (rgAN = 0.26 vs. rgPT = −0.20). In Part 2, individuals with adolescent persistent thinness in the ALSPAC had lower borderline personality disorder polygenic scores (OR = 0.77; Q = 0.01). Overall, results suggest that genetic variants associated with thinness are negatively associated with psychiatric disorders and therefore thinness may be differentiable from anorexia nervosa on a genomic level.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Human Genetics |
| Vol/bind | 32 |
| Udgave nummer | 1 |
| Sider (fra-til) | 117-124 |
| ISSN | 1018-4813 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
This study represents independent research funded in part by the UK National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the UK NHS, the NIHR or the Department of Health. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). This work was supported by the UK Medical Research Council and the Medical Research Foundation (ref: MR/R004803/1). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2 and 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ); This research was specifically funded by the NIHR (CS/01/2008/014), the NIH (MH087786-01). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. NM and CB acknowledge funding from the National Institute of Mental Health (R21 MH115397). The Anorexia Nervosa Genetics Initiative (ANGI) is an initiative of the Klarman Family Foundation. CMB is supported by NIMH (R01MH120170; R01MH124871; R01MH119084; R01MH118278; R01 MH124871); Brain and Behavior Research Foundation Distinguished Investigator Grant; Swedish Research Council (Vetenskapsrådet, award: 538-2013-8864); CMB and CH are supported by Lundbeck Foundation (Grant no. R276-2018-4581). MH is supported by a fellowship from the Medical Research Council UK (MR/T027843/1). NM was supported by a Brain and Behavior Research Foundation Independent Investigator award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders were not involved in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.
Publisher Copyright:
© 2023, The Author(s).
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