Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci
Year: 2016
Type: review
Study design: Observational Study
Abstract: 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.
Source: PLoS Genetics
Authors: 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
Institutions: University of Exeter, 23andMe (United States), Estonian Biocentre, University of Tartu, Institute of Genetics and Cancer, MRC Human Genetics Unit, Institut für Medizinische Psychologie, Ludwig-Maximilians-Universität München, University of Edinburgh, Eurac Research, University of Lübeck, Korea University Ansan Hospital, Seoul National University Bundang Hospital, The University of Queensland, University of Pennsylvania, Erasmus MC
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,187
Awards: G1058688197, The causes of hyperglycaemia in the face of rising obesity, G2075718497, Identifying non-coding mutations in early-onset diabetes, Using genetics to understand how the maternal intrauterine environment influences fetal growth., G6155866834, Using genetics to understand how the maternal intrauterine environment influences fetal growth., G7133053097, G7283484021, G7684670512, G843141311, G8737378601
OpenAlex ID: W2491330173