TY - JOUR
T1 - Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci
AU - Jones, Samuel E.
AU - Tyrrell, Jessica
AU - Wood, Andrew R.
AU - Beaumont, Robin N.
AU - Ruth, Katherine S.
AU - Tuke, Marcus A.
AU - Yaghootkar, Hanieh
AU - Hu, Youna
AU - Teder-Laving, Maris
AU - Hayward, Caroline
AU - Roenneberg, Till
AU - Wilson, James F.
AU - Del Greco, Fabiola
AU - Hicks, Andrew A.
AU - Shin, Chol
AU - Yun, Chang Ho
AU - Lee, Seung Ku
AU - Metspalu, Andres
AU - Byrne, Enda M.
AU - Gehrman, Philip R.
AU - Tiemeier, Henning
AU - Allebrandt, Karla V.
AU - Freathy, Rachel M.
AU - Murray, Anna
AU - Hinds, David A.
AU - Frayling, Timothy M.
AU - Weedon, Michael N.
N1 - Funding Information:
This 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.
Publisher Copyright:
© 2016 Jones et al.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84984916617&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1006125
DO - 10.1371/journal.pgen.1006125
M3 - Article
C2 - 27494321
AN - SCOPUS:84984916617
SN - 1553-7390
VL - 12
JO - PLoS Genetics
JF - PLoS Genetics
IS - 8
M1 - e1006125
ER -
