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

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

doi:10.1038/ncomms10889

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.

Highlights

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock
Despite the importance of circadian rhythms to human health and their fundamental role demonstrated in model organisms[4,5], little is known about the biological mechanisms underlying inter-individual variation in human chronotype or how it impacts our health and physiology
No significant associations were observed (Supplementary Table 13). In this largest genome-wide association study (GWAS) of chronotype to date, we report the discovery of 12 genetic loci associated with chronotype, and pathway analysis suggests key roles of genes in the nervous and ocular systems

Summary

Introduction

Chronotype, is a manifestation of our internal biological clock. To define the spectrum of genetic variation contributing to variation in human circadian phenotype, and identify associative or causal links between chronotype and other health indices, we perform the largest GWAS of self-reported chronotype to date, within the UK Biobank cohort (n 1⁄4 100,420), a unique resource with an extensive set of individual life history parameters.

Results

Conclusion