Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.
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-reporte...
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Public Library of Science (PLoS)
2016-08-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006125&type=printable |
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| author | Samuel E Jones Jessica Tyrrell Andrew R Wood Robin N Beaumont Katherine S Ruth Marcus A Tuke Hanieh Yaghootkar Youna Hu Maris Teder-Laving Caroline Hayward Till Roenneberg James F Wilson Fabiola Del Greco Andrew A Hicks Chol Shin Chang-Ho Yun Seung Ku Lee Andres Metspalu Enda M Byrne Philip R Gehrman Henning Tiemeier Karla V Allebrandt Rachel M Freathy Anna Murray David A Hinds Timothy M Frayling Michael N Weedon |
| author_facet | Samuel E Jones Jessica Tyrrell Andrew R Wood Robin N Beaumont Katherine S Ruth Marcus A Tuke Hanieh Yaghootkar Youna Hu Maris Teder-Laving Caroline Hayward Till Roenneberg James F Wilson Fabiola Del Greco Andrew A Hicks Chol Shin Chang-Ho Yun Seung Ku Lee Andres Metspalu Enda M Byrne Philip R Gehrman Henning Tiemeier Karla V Allebrandt Rachel M Freathy Anna Murray David A Hinds Timothy M Frayling Michael N Weedon |
| author_sort | Samuel E Jones |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-80eac3f9df0149afabc3a13a112d8fb9 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2016-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-80eac3f9df0149afabc3a13a112d8fb92025-08-20T03:26:09ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-08-01128e100612510.1371/journal.pgen.1006125Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.Samuel E JonesJessica TyrrellAndrew R WoodRobin N BeaumontKatherine S RuthMarcus A TukeHanieh YaghootkarYouna HuMaris Teder-LavingCaroline HaywardTill RoennebergJames F WilsonFabiola Del GrecoAndrew A HicksChol ShinChang-Ho YunSeung Ku LeeAndres MetspaluEnda M ByrnePhilip R GehrmanHenning TiemeierKarla V AllebrandtRachel M FreathyAnna MurrayDavid A HindsTimothy M FraylingMichael N WeedonDisrupted 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006125&type=printable |
| spellingShingle | Samuel E Jones Jessica Tyrrell Andrew R Wood Robin N Beaumont Katherine S Ruth Marcus A Tuke Hanieh Yaghootkar Youna Hu Maris Teder-Laving Caroline Hayward Till Roenneberg James F Wilson Fabiola Del Greco Andrew A Hicks Chol Shin Chang-Ho Yun Seung Ku Lee Andres Metspalu Enda M Byrne Philip R Gehrman Henning Tiemeier Karla V Allebrandt Rachel M Freathy Anna Murray David A Hinds Timothy M Frayling Michael N Weedon Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci. PLoS Genetics |
| title | Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci. |
| title_full | Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci. |
| title_fullStr | Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci. |
| title_full_unstemmed | Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci. |
| title_short | Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci. |
| title_sort | genome wide association analyses in 128 266 individuals identifies new morningness and sleep duration loci |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006125&type=printable |
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