Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Jacqueline M. Lane, Irma Vlasac, Simon G. Anderson, Simon D. Kyle, William G. Dixon, David A. Bechtold, Shubhroz Gill, Max A. Little, Annemarie Luik, Andrew Loudon, Richard Emsley, Frank A.J.L. Scheer, Deborah A. Lawlor, Susan Redline, David W. Ray, Martin K. Rutter, Richa Saxena*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.

Original languageEnglish
Article number10889
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 9 Mar 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by NIH grants R21HL121728-02 (R.S.), F32DK102323-01A1 (J.M.L.), R01HL113338-04 (J.M.L., S.R. and R.S.), the University of Manchester (Research Infrastructure Fund), the Wellcome Trust (salary support D.W.R. and A.L.) and UK Medical Research Council MC_UU_12013/5 (D.A.L.). Data on glycemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org. Data on coronary artery disease/myocardial infarction have been contributed by CARDIo-GRAMplusC4D investigators and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. We thank the International Genomics of Alzheimer’s Project (IGAP) for providing summary results data for these analyses.

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