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

Nat Commun 2016 Mar 9;7:10889. Epub 2016 Mar 9.

Center for Human Genetic Research Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

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.

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http://dx.doi.org/10.1038/ncomms10889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786869PMC
March 2016
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References

(Supplied by CrossRef)

A Adan et al.
Chronobiol. Int. 2012

JS Takahashi et al.
Nat. Rev. Genet. 2008

RG Foster et al.
Prog. Mol. Biol. Transl. Sci. 2013

D Bell-Pedersen et al.
Nat. Rev. Genet. 2005

T Roenneberg et al.
Sleep Med .Rev. 2007

RL Sack et al.
Sleep 2007

CR Jones et al.
Nat. Med. 1999

Y Xu et al.
Cell 2007

CE Gamaldo et al.
J. Am. Soc. Hypertens. 2014

KC Brennan et al.
Sci. Transl. Med. 2013

C Saini et al.
Front. Neurol. 2015

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