Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms
Year: 2019
Type: article
Study design: Observational Study
Abstract: Being a morning person is a behavioural indicator of a person's underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.
Source: Nature Communications
Authors: Samuel E. Jones, Jacqueline M. Lane, Andrew R. Wood, Vincent T. van Hees, Jessica Tyrrell, Robin N. Beaumont, Aaron R. Jeffries, Hassan S. Dashti, Melvyn Hillsdon, Katherine S. Ruth, Marcus A. Tuke, Hanieh Yaghootkar, Seth A. Sharp, Yingjie Jie, William D. Thompson, Jamie W. Harrison, Amy Dawes, Enda M. Byrne, Henning Tiemeier, Karla V. Allebrandt, Jack Bowden, David W. Ray, Rachel M. Freathy, Anna Murray, Diego R. Mazzotti, Philip R. Gehrman, Debbie A. Lawlor, Timothy M. Frayling, Martin K. Rutter, David A. Hinds, Richa Saxena, Michael N. Weedon
Institutions: University of Exeter, Royal Devon and Exeter Hospital, Exeter Hospital, Broad Institute, Harvard University, Massachusetts General Hospital, Netherlands eScience Center, The University of Queensland, Institute for Molecular Bioscience, Erasmus MC, Sanofi (Germany), University of Bristol, MRC Integrative Epidemiology Unit, University of Manchester, University of Pennsylvania, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, 23andMe (United States), Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Royal Devon & Exeter NHS Foundation Trust
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,856
Funders: Wellcome Trust, National Institute for Health and Care Research, Diabetes Research and Wellness Foundation, University of Manchester, European Commission, University of Bristol, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, FP7 Ideas: European Research Council, Common Fund
Awards: Reproductive and cardio-metabolic health, The causes of hyperglycaemia in the face of rising obesity, NIHR Senior Investigator Award, G1992394716, G2190462495, Identifying non-coding mutations in early-onset diabetes, G2786058305, Impact of Malatonin, Food Timing and Receptor Variant on Type 2 Diabetes Risk, G3201713599, G3207356259, The genetics of sleep patterns and their relationship to obesity and Type 2 diabetes, Using genomics to understand psychiatric disorders, Using genetics to understand how the maternal intrauterine environment influences fetal growth., Postpartum Depression: Action Towards Causes and Treatment, G4089438869, Multivariate whole genome estimation and prediction analysis of genomics data applied to psychiatric disorders, Clock control of inflammation in the lung., G4793289069, Clock control of inflammation in the lung., G5260012927, UK Biobank (core renewal), Melatonin and Receptor Gene Variant: Linking Circadian System and Type 2 Diabetes, Statistical Methods for Improving Causal Analyses, G5414291753, G5834621717, Inflammatory therapeutics and the role of the circadian clock, G6050707053, G6251221280, G642847709, Using genetics to understand how the maternal intrauterine environment influences fetal growth., G7283484021, G7546946110, Genetic and molecular basis of circadian rhythm disorders, G8130967345, G843141311, G8502142660, G8737378601, Impact of genetic variants on sleep timing and type 2 diabetes risk, Pleiotropy robust Mendelian randomization, G896728979, Training in Sleep, Circadian, and Respiratory Neurobiology, Genetics of chronotype and impact on metabolic disease
OpenAlex ID: W2914232633