TY - JOUR T1 - Genome-wide association analyses in > 119,000 individuals identifies thirteen morningness and two sleep duration loci JF - bioRxiv DO - 10.1101/031369 SP - 031369 AU - Samuel E. Jones AU - Jessica Tyrrell AU - Andrew R. Wood AU - Robin N. Beaumont AU - Katherine S. Ruth AU - Marcus A. Tuke AU - Hanieh Yaghootkar AU - Youna Hu AU - Maris Teder-Laving AU - Caroline Hayward AU - Till Roenneberg AU - James F. Wilson AU - Fabiola Del Greco AU - Andrew A. Hicks AU - Chol Shin AU - Chang-Ho Yun AU - Seung Ku Lee AU - Andres Metspalu AU - Enda M. Byrne AU - Philip R. Gehrman AU - Henning Tiemeier AU - Karla V. Allebrandt AU - Rachel M. Freathy AU - Anna Murray AU - David A. Hinds AU - Timothy M. Frayling AU - Michael N. Weedon Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/02/02/031369.abstract N2 - Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but little is 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 89,823 23andMe participants; thirteen of the chronotype signals remained significant at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. For sleep duration, we replicated one known signal in PAX8 (2.6 [95%CIs 1.9, 3.2] minutes per allele P=5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 [95% CI: 1.3, 2.7] minutes per allele, P=1.2x10-9; and 1.6 [95% CI: 1.1, 2.2] minutes per allele, P=7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG=0.056, P=0.048); undersleeping and BMI (rG=0.147, P=1x10-5) and oversleeping and BMI (rG=0.097, P=0.039), Mendelian Randomisation analyses provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study provides new insights into the biology of sleep and circadian rhythms in humans. ER -