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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 M F
dc.contributor.authorHicks AA
dc.contributor.authorShin C
dc.contributor.authorYun CH
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.accessioned2018-10-08T13:50:14Z
dc.date.available2018-10-08T13:50:14Z
dc.date.issued2016
dc.identifier.issn1553-7390
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pgen.1006125
dc.identifier.urihttp://hdl.handle.net/10863/6435
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_US
dc.language.isoenen_US
dc.rights
dc.titleGenome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Locien_US
dc.typeArticleen_US
dc.date.updated2018-10-08T13:48:51Z
dc.language.isiEN-GB
dc.journal.titlePLoS genetics
dc.description.fulltextopenen_US


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