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 cardio-metabolic diseases, psychiatric disorders and all-cause mortality1,2, affect 25–30% of adults worldwide3. While environmental factors contribute importantly to self-reported habitual sleep duration and disruption, these traits are heritable4–9, and gene identification should improve our understanding of sleep function, mechanisms linking sleep to disease, and development of novel therapies. We report single and multi-trait genome-wide association analyses (GWAS) of self-reported sleep duration, insomnia symptoms including difficulty initiating and/or maintaining sleep, and excessive daytime sleepiness in the UK Biobank (n=112,586), with discovery of loci for insomnia symptoms (near MEIS1, TMEM132E, CYCL1, TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR/OPHN1) and a composite sleep trait (near INADL and HCRTR2), as well as replication of a locus for sleep duration (at PAX-8). Genetic correlation was observed between longer sleep duration and schizophrenia (rG=0.29, p=1.90x10−13) and between increased excessive daytime sleepiness and increased adiposity traits (BMI rG=0.20, p=3.12x10−09; waist circumference rG=0.20, p=2.12x10−07).