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dc.contributor.authorJones, SE
dc.contributor.authorTyrrell, J
dc.contributor.authorWood, AR
dc.contributor.authorBeaumont, RN
dc.contributor.authorRuth, KS
dc.contributor.authorTuke, MA
dc.contributor.authorYaghootkar, H
dc.contributor.authorHu, Y
dc.contributor.authorTeder-Laving, M
dc.contributor.authorHayward, C
dc.contributor.authorRoenneberg, T
dc.contributor.authorWilson, JF
dc.contributor.authorDel Greco, F
dc.contributor.authorHicks, AA
dc.contributor.authorShin, C
dc.contributor.authorYun, C-H
dc.contributor.authorLee, SK
dc.contributor.authorMetspalu, A
dc.contributor.authorByrne, EM
dc.contributor.authorGehrman, PR
dc.contributor.authorTiemeier, H
dc.contributor.authorAllebrandt, KV
dc.contributor.authorFreathy, RM
dc.contributor.authorMurray, A
dc.contributor.authorHinds, DA
dc.contributor.authorFrayling, TM
dc.contributor.authorWeedon, MN
dc.date.accessioned2016-07-01T12:00:08Z
dc.date.issued2016-08-05
dc.description.abstractDisrupted 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.en_GB
dc.description.sponsorshipThis research has been conducted using the UK Biobank Resource. This study was provided with biospecimens and data from the Korean Genome Analysis Project (4845-301), the Korean Genome and Epidemiology Study (2010-E71001-00, 2011-E71004-00, and 2011-E71008-00), and Korea Biobank Project (4851-307) that were supported by the Korea Centers for Disease Control & Prevention (URL: http://www.cdc.go.kr/CDC/eng/main.jsp), Republic of Korea. We would also like to thank the research participants and employees of 23andMe for making this work possible.en_GB
dc.identifier.citationPLoS Genetics, 2016, 12(8): e1006125
dc.identifier.doi10.1371/journal.pgen.1006125
dc.identifier.urihttp://hdl.handle.net/10871/22352
dc.language.isoenen_GB
dc.publisherPublic Library of Scienceen_GB
dc.rightsThis is the author accepted manuscript. The final version is available from PLoS via the DOI in this record.
dc.titleGenome-wide association analyses in 128,266 individuals identifies new morningness and sleep duration locien_GB
dc.typeArticleen_GB
dc.identifier.issn1553-7404
dc.identifier.journalPLoS Geneticsen_GB


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