Genome-wide association analyses in 128,266 individuals identifies new morningness and sleep duration loci

Jones, Samuel E., Tyrrell, Jessica, Wood, Andrew R., Beaumont, Robin N., Ruth, Katherine S., Tuke, Marcus A., Yaghootkar, Hanieh, Hu, Youna, Teder-Laving, Maris, Hayward, Caroline, Roenneberg, Till, Wilson, James F., Del Greco, Fabiola, Hicks, Andrew A., Shin, Chol, Yun, Chang-Ho, Lee, Seung Ku, Metspalu, Andres, Byrne, Enda M., Gehrman, Philip R., Tiemeier, Henning, Allebrandt, Karla V., Freathy, Rachel M., Murray, Anna, Hinds, David A., Frayling, Timothy M. and Weedon, Michael N. (2016) Genome-wide association analyses in 128,266 individuals identifies new morningness and sleep duration loci. PLoS Genetics, 12 8: . doi:10.1371/journal.pgen.1006125

Author Jones, Samuel E.
Tyrrell, Jessica
Wood, Andrew R.
Beaumont, Robin N.
Ruth, Katherine S.
Tuke, Marcus A.
Yaghootkar, Hanieh
Hu, Youna
Teder-Laving, Maris
Hayward, Caroline
Roenneberg, Till
Wilson, James F.
Del Greco, Fabiola
Hicks, Andrew A.
Shin, Chol
Yun, Chang-Ho
Lee, Seung Ku
Metspalu, Andres
Byrne, Enda M.
Gehrman, Philip R.
Tiemeier, Henning
Allebrandt, Karla V.
Freathy, Rachel M.
Murray, Anna
Hinds, David A.
Frayling, Timothy M.
Weedon, Michael N.
Title Genome-wide association analyses in 128,266 individuals identifies new morningness and sleep duration loci
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7404
Publication date 2016-08-05
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1006125
Open Access Status DOI
Volume 12
Issue 8
Total pages 19
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 02 Oct 2016, 10:30:12 EST by System User on behalf of Learning and Research Services (UQ Library)