Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits

Jacqueline Lane, Jingjing Liang, Irma Vlasac, Simon G Anderson, David A Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A Little, AnneMarie I Luik, Andrew Loudon, Frank A J L Scheer, Shaun M Purcell, Simon D Kyle, Debbie Lawlor, Xiaofeng Zhu, Susan Redline, David W Ray, Martin K Rutter , Richa Saxena

Research output: Contribution to journalArticle (Academic Journal)

108 Citations (Scopus)
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Abstract

Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality1, 2, affect 25–30% of adults worldwide3. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable4, 5, 6, 7, 8, 9 and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR–OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10−13) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10−9; waist circumference: rg = 0.20, P = 2.12 × 10−7).
Original languageEnglish
Pages (from-to)274–281
Number of pages10
JournalNature Genetics
Volume49
Issue number2
Early online date19 Dec 2016
DOIs
Publication statusPublished - 1 Feb 2017

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  • Projects

    Jack Bowden fellowship transfer

    Gaunt, L. F.

    1/08/1531/03/18

    Project: Research

    MRC UoB UNITE Unit - Programme 5

    Lawlor, D. A. & Lawlor, D. A.

    1/06/1331/03/18

    Project: Research

    IEU Theme 3

    Windmeijer, F., Tilling, K. M. & Tilling, K. M.

    1/06/1331/03/18

    Project: Research

    Cite this

    Lane, J., Liang, J., Vlasac, I., Anderson, S. G., Bechtold, D. A., Bowden, J., Emsley, R., Gill, S., A Little, M., Luik, A. I., Loudon, A., Scheer, F. A. J. L., Purcell, S. M., Kyle, S. D., Lawlor, D., Zhu, X., Redline, S., Ray, D. W., Rutter , M. K., & Saxena, R. (2017). Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. Nature Genetics, 49(2), 274–281. https://doi.org/10.1038/ng.3749