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PLoS Genet. 2016 Aug 5;12(8):e1006125. doi: 10.1371/journal.pgen.1006125. eCollection 2016 Aug.

Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.

Author information

1
Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.
2
23andMe Inc., Mountain View, California, United States of America.
3
A9.com Inc, Palo Alto, California, United States of America.
4
Estonian Genome Center and Institute of Molecular and Cell Biology of University of Tartu, Estonian Biocentre, Tartu, Estonia.
5
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, Scotland.
6
Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany.
7
Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
8
Center for Biomedicine, European Academy of Bolzano, Bozen, Italy-affiliated Institute of the University of Lübeck, Lübeck, Germany.
9
Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.
10
Institute of Human Genomic Study, College of Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.
11
Department of Neurology, Bundang Clinical Neuroscience Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
12
The University of Queensland, Queensland Brain Institute, Brisbane, Australia.
13
Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
14
Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
15
Department of Psychiatry, Erasmus Medical Center, Rotterdam, Netherlands.

Abstract

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans.

PMID:
27494321
PMCID:
PMC4975467
DOI:
10.1371/journal.pgen.1006125
[Indexed for MEDLINE]
Free PMC Article

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