Genome-wide association analysis of excessive daytime sleepiness identifies 42 loci that suggest phenotypic subgroups
Jacqueline M. Lane,
Samuel E. Jones,
Hassan S Dashti,
Andrew R. Wood,
Vincent T. van Hees,
Bendik S Winsvold,
Brian E. Cade,
Simon G Anderson,
David A. Bechtold,
Simon D Kyle,
Max A Little,
Andrew S Loudon,
Frank AJL Scheer,
Shaun M. Purcell,
Rebecca C. Richmond,
Jonas B. Nielsen,
Cristen J. Willer,
Linn B. Strand,
David W. Ray,
Deborah A. Lawlor,
Martin K Rutter,
Michael N Weedon,
Posted 26 Oct 2018
bioRxiv DOI: 10.1101/454561 (published DOI: 10.1038/s41467-019-11456-7)
Posted 26 Oct 2018
Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. We identified 42 loci for self-reported EDS in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirmed the aggregate effect of a genetic risk score of 42 SNPs on EDS in independent Scandinavian cohorts and on other sleep disorders (restless leg syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). Strong genetic correlations were also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing. EDS variants clustered into two predominant composite phenotypes - sleep propensity and sleep fragmentation - with the former showing stronger evidence for enriched expression in central nervous system tissues, suggesting two unique mechanistic pathways. Mendelian randomization analysis indicated that higher BMI is causally associated with EDS risk, but EDS does not appear to causally influence BMI.
- Downloaded 532 times
- Download rankings, all-time:
- Site-wide: 33,721 out of 101,039
- In genomics: 3,317 out of 6,265
- Year to date:
- Site-wide: 78,879 out of 101,039
- Since beginning of last month:
- Site-wide: 79,258 out of 101,039
Downloads over time
Distribution of downloads per paper, site-wide
- 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!