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

Lane JM., Liang J., Vlasac I., Anderson SG., Bechtold DA., Bowden J., Emsley R., Gill S., Little MA., Luik AI., Loudon A., Scheer FAJL., Purcell SM., Kyle SD., Lawlor DA., Zhu X., Redline S., Ray DW., Rutter MK., Saxena R.

Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable 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).

DOI

10.1038/ng.3749

Type

Journal article

Journal

Nat Genet

Publication Date

02/2017

Volume

49

Pages

274 - 281

Keywords

Adiposity, Adult, Aged, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Mental Disorders, Metabolic Diseases, Middle Aged, Phenotype, Self Report, Sleep, Sleep Wake Disorders, Waist Circumference

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