Genome-wide association analyses in > 119,000 individuals identifies thirteen morningness and two sleep duration loci

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.