Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent

Christopher Hübel; Héléna A Gaspar; Jonathan R I Coleman; Ken B Hanscombe; Kirstin Purves; INGA PROKOPENKO; Mariaelisa Graff; Julius S Ngwa; Tsegaselassie Workalemahu; Paul O'Reilly; Cynthia M Bulik; Gerome Breen

doi:10.1038/s41467-019-13544-0

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Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent

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Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent

Christopher Hübel, Héléna A Gaspar, Jonathan R I Coleman, Ken B Hanscombe, Kirstin Purves, INGA PROKOPENKO, Mariaelisa Graff, Julius S Ngwa, Tsegaselassie Workalemahu, Paul O'Reilly, …

Nature communications, Vol.10, 5765

18/12/2019

DOI: https://doi.org/10.1038/s41467-019-13544-0

PMCID: PMC6920448

PMID: 31852892

Abstract

Age Factors

Blood Glucose - genetics

Body Composition - genetics

Educational Status

Female

Genetic Variation

Genome-Wide Association Study

Humans

Male

Mental Disorders - epidemiology

Mental Disorders - genetics

Mental Disorders - prevention & control

Middle Aged

Multifactorial Inheritance - genetics

Overweight - epidemiology

Overweight - genetics

Risk Factors

Sex Factors

Comorbidity

Phenotype

Physical Fitness

Body composition is often altered in psychiatric disorders. Using genome-wide common genetic variation data, we calculate sex-specific genetic correlations amongst body fat %, fat mass, fat-free mass, physical activity, glycemic traits and 17 psychiatric traits (up to N = 217,568). Two patterns emerge: (1) anorexia nervosa, schizophrenia, obsessive-compulsive disorder, and education years are negatively genetically correlated with body fat % and fat-free mass, whereas (2) attention-deficit/hyperactivity disorder (ADHD), alcohol dependence, insomnia, and heavy smoking are positively correlated. Anorexia nervosa shows a stronger genetic correlation with body fat % in females, whereas education years is more strongly correlated with fat mass in males. Education years and ADHD show genetic overlap with childhood obesity. Mendelian randomization identifies schizophrenia, anorexia nervosa, and higher education as causal for decreased fat mass, with higher body fat % possibly being a causal risk factor for ADHD and heavy smoking. These results suggest new possibilities for targeted preventive strategies.

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Title: Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent
Creators: Christopher Hübel - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Solna, Sweden. christopher.huebel@ki.se
Héléna A Gaspar - UK National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), South London and Maudsley NHS Foundation Trust, London, SE5 8AF, UK
Jonathan R I Coleman - UK National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), South London and Maudsley NHS Foundation Trust, London, SE5 8AF, UK
Ken B Hanscombe - Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, SE1 9RT, UK
Kirstin Purves - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK
INGA PROKOPENKO (Author)
Mariaelisa Graff - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27516, USA
Julius S Ngwa - Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA
Tsegaselassie Workalemahu - Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA
Paul O'Reilly - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK
Cynthia M Bulik - Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, 27599, NC, USA
Gerome Breen - UK National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), South London and Maudsley NHS Foundation Trust, London, SE5 8AF, UK
Publication Details: Nature communications, Vol.10, 5765
Publisher: Nature Research
Publication Date: 18/12/2019
Date accepted for publication: 08/11/2019
Grants: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic non-communicable diseases, 874739, European Commission (Belgium, Brussels) - EC
Grant note: This study represents independent research part funded 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 and Social Care. High-performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). Research reported in this publication was supported by the USA National Institute of Mental Health of the National Institutes of Health (NIMH) under Award Number U01 MH109514, U01 MH109528, U01 MH109514 and U01 MH109536. The PGC Substance Use Disorders group acknowledges support from MH109532. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Prof. Bulik acknowledges funding from the Swedish Research Council (VR Dnr: 538-2013-8864) and the Klarman Family Foundation (the Anorexia Nervosa Genetics Initiative is an initiative of the Klarman Family Foundation). Profs. Bulik and Micali are supported by NIMH R21 MH115397. PFO receives funding from the UK Medical Research Council (MR/N015746/1) and the Wellcome Trust (109863/Z/15/Z). Dr. Graff acknowledges funding from the National Institutes of Health (R01HD057194). Dr. Workalemahu acknowledges funding by the Intramural Research Programme of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Dr. Prokopenko was funded by the European Union’s Horizon 2020 research, and innovation programme (LONGITOOLS, H2020-SC1-2019-874739; DYNAhealth, H2020-PHC-2014-633595); and the Wellcome Trust (WT205915). Data on glycaemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org. Data on the childhood BMI trait has been contributed by the EGG Consortium and has been downloaded from www.egg-consortium.org. This study was completed as part of approved UK Biobank study application 27546 to Dr. Breen. Open access funding provided by Karolinska Institute.
Identifiers: 99594523302346; WOS:000503222500001
Copyright: © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article
SDG (Scopus 2023): SDG 3

Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent

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