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GWAS identifies 10 loci for objectively-measured physical activity and sleep with causal roles in cardiometabolic disease

View ORCID ProfileAiden Doherty, Karl Smith-Byrne, Teresa Ferreira, View ORCID ProfileMichael V. Holmes, View ORCID ProfileChris Holmes, View ORCID ProfileSara L. Pulit, View ORCID ProfileCecilia M. Lindgren
doi: https://doi.org/10.1101/261719
Aiden Doherty
1Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, U.K.
2Nuffield Department of Population Health, BHF Centre of Research Excellence, University of Oxford, Oxford, U.K.
3Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, U.K.
4NIHR Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK
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  • For correspondence: aiden.doherty@bdi.ox.ac.uk
Karl Smith-Byrne
5Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
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Teresa Ferreira
1Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, U.K.
6Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
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Michael V. Holmes
4NIHR Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK
7Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
8Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
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Chris Holmes
1Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, U.K.
9Department of Statistics, University of Oxford, Oxford, UK
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Sara L. Pulit
1Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, U.K.
6Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
10Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
11Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
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Cecilia M. Lindgren
1Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, U.K.
4NIHR Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK
6Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
11Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
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ABSTRACT

Physical activity and sleep disorders are established risk factors for many diseases, but their etiology is poorly understood, partly due to a reliance on self-reported evidence. Here we report a genome-wide association study (GWAS) of wearable-defined and machine-learned physical activity and sleep phenotypes in 91,112 UK Biobank participants, and self-reported physical activity in 351,154 UK Biobank participants. While the self-reported activity analysis resulted in no significant (p<5×10−9) loci, the analysis of objectively-measured traits identified 10 loci, 6 of which are novel. These 10 loci account for 0.05% of activity and 0.33% of sleep phenotype variation, but genome-wide estimates suggest that common variation accounts for ~12% of phenotypic variation, indicating high polygenicity. Heritability was higher in women than in men for overall activity (Δh2 = 4%, p=6.3×10−5), moderate intensity activity (6%, p=6.7×10−8), and walking (5%, p=2.6×10−6). Heritability partitioning, enrichment and pathway analyses all indicate the central nervous system plays a role in activity behaviours. Mendelian randomization in publicly available GWAS data and in 278,367 UK Biobank participants, who were not included in our discovery analyses, suggest that overall activity might be causally related to lowering body fat percentage (beta per SD higher overall activity: −0.44, SE=0.047, p=2.70×10−21) and systolic blood pressure (beta per SD: −0.71, SE=0.125, p=1.38×10−8). Our current results advocate the value of physical activity for the reduction of adiposity and blood pressure.

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Posted February 08, 2018.
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GWAS identifies 10 loci for objectively-measured physical activity and sleep with causal roles in cardiometabolic disease
Aiden Doherty, Karl Smith-Byrne, Teresa Ferreira, Michael V. Holmes, Chris Holmes, Sara L. Pulit, Cecilia M. Lindgren
bioRxiv 261719; doi: https://doi.org/10.1101/261719
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GWAS identifies 10 loci for objectively-measured physical activity and sleep with causal roles in cardiometabolic disease
Aiden Doherty, Karl Smith-Byrne, Teresa Ferreira, Michael V. Holmes, Chris Holmes, Sara L. Pulit, Cecilia M. Lindgren
bioRxiv 261719; doi: https://doi.org/10.1101/261719

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