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

Lane, Jacqueline M., Vlasac, Irma, Anderson, Simon G., Kyle, Simon D., Dixon, William G., Bechtold, David A., Gill, Shubhroz, Little, Max A., Luik, Annemarie, Loudon, Andrew, Emsley, Richard, Scheer, Frank A.J.L., Lawlor, Deborah A., Redline, Susan, Ray, David W., Rutter, Martin K. and Saxena, Richa (2016). Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank. Nature Communications, 7 ,

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.

Publication DOI: https://doi.org/10.1038/ncomms10889
Divisions: Engineering & Applied Sciences > Mathematics
Engineering & Applied Sciences > Systems analytics research institute (SARI)
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Funding: NIH (R21HL121728-02, F32DK102323-01A1 and R01HL113338-04); University of Manchester (Research Infrastructure Fund); Wellcome Trust; and MRC (MC_UU_12013/5 (D.A.L.). Supplementary data availalbe on the journal website.
Uncontrolled Keywords: Biochemistry, Genetics and Molecular Biology(all),Chemistry(all),Physics and Astronomy(all)
Full Text Link: http://www.natu ... comms10889.html
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2016-03-09
Authors: Lane, Jacqueline M.
Vlasac, Irma
Anderson, Simon G.
Kyle, Simon D.
Dixon, William G.
Bechtold, David A.
Gill, Shubhroz
Little, Max A. ( 0000-0002-1507-3822)
Luik, Annemarie
Loudon, Andrew
Emsley, Richard
Scheer, Frank A.J.L.
Lawlor, Deborah A.
Redline, Susan
Ray, David W.
Rutter, Martin K.
Saxena, Richa

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