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Nat Commun. 2016 Mar 9;7:10889. doi: 10.1038/ncomms10889.

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank.

Author information

1
Center for Human Genetic Research Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
2
Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
3
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
4
Cardiovascular Research Group, Institute of Cardiovascular Sciences, The University of Manchester, Manchester M139PL, UK.
5
Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX12JD, UK.
6
Centre for Musculoskeletal Research Institute of Inflammation and Repair, The University of Manchester, Manchester M139PL, UK.
7
Faculty of Life Sciences, The University of Manchester, Manchester M139PL, UK.
8
Chemical Biology Program, Broad Institute, Cambridge, Massachusetts 02142, USA.
9
Department of Mathematics, Engineering and Applied Science, Aston University, Birmingham B47ET, UK.
10
Institute of Population Health, The University of Manchester, Manchester M139PL, UK.
11
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
12
Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
13
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol BS81TH, UK.
14
School of Social and Community Medicine, University of Bristol, Bristol BS81TH, UK.
15
Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester M139PL, UK.
16
Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M139PL, UK.

Abstract

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.

PMID:
26955885
PMCID:
PMC4786869
DOI:
10.1038/ncomms10889
[Indexed for MEDLINE]
Free PMC Article

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