Novel Loci Associated with Usual Sleep Duration: The CHARGE Consortium Genome-Wide Association Study
Rimm, Eric Bruce::0ab2926c8242f35e5a982e3cf59f4987::600
Uitterlinden, André G.
O’Connor, George T.
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CitationGottlieb, D J, K Hek, T-h Chen, N F Watson, G Eiriksdottir, E M Byrne, M Cornelis, et al. 2014. “Novel Loci Associated with Usual Sleep Duration: The CHARGE Consortium Genome-Wide Association Study.” Molecular Psychiatry 20 (10): 1232–39. https://doi.org/10.1038/mp.2014.133.
AbstractUsual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P = 1.1 x 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P = 9.3 x 10(-4)). The strongest combined association was at rs1823125 (P = 1.5 x 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.
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