학술논문
Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study
Document Type
article
Author
Gottlieb, DJ; Hek, K; Chen, T-H; Watson, NF; Eiriksdottir, G; Byrne, EM; Cornelis, M; Warby, SC; Bandinelli, S; Cherkas, L; Evans, DS; Grabe, HJ; Lahti, J; Li, M; Lehtimäki, T; Lumley, T; Marciante, KD; Pérusse, L; Psaty, BM; Robbins, J; Tranah, GJ; Vink, JM; Wilk, JB; Stafford, JM; Bellis, C; Biffar, R; Bouchard, C; Cade, B; Curhan, GC; Eriksson, JG; Ewert, R; Ferrucci, L; Fülöp, T; Gehrman, PR; Goodloe, R; Harris, TB; Heath, AC; Hernandez, D; Hofman, A; Hottenga, J-J; Hunter, DJ; Jensen, MK; Johnson, AD; Kähönen, M; Kao, L; Kraft, P; Larkin, EK; Lauderdale, DS; Luik, AI; Medici, M; Montgomery, GW; Palotie, A; Patel, SR; Pistis, G; Porcu, E; Quaye, L; Raitakari, O; Redline, S; Rimm, EB; Rotter, JI; Smith, AV; Spector, TD; Teumer, A; Uitterlinden, AG; Vohl, M-C; Widen, E; Willemsen, G; Young, T; Zhang, X; Liu, Y; Blangero, J; Boomsma, DI; Gudnason, V; Hu, F; Mangino, M; Martin, NG; O'Connor, GT; Stone, KL; Tanaka, T; Viikari, J; Gharib, SA; Punjabi, NM; Räikkönen, K; Völzke, H; Mignot, E; Tiemeier, H
Source
Molecular Psychiatry. 20(10)
Subject
Language
Abstract
Usual 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 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 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.