Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02215, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02141, USA.
Hum Mol Genet. 2023 Sep 5;32(18):2797-2807. doi: 10.1093/hmg/ddad101.
Both short (≤6 h per night) and long sleep duration (≥9 h per night) are associated with increased risk of chronic diseases. Despite evidence linking habitual sleep duration and risk of disease, the genetic determinants of sleep duration in the general population are poorly understood, especially outside of European (EUR) populations. Here, we report that a polygenic score of 78 European ancestry sleep duration single-nucleotide polymorphisms (SNPs) is associated with sleep duration in an African (n = 7288; P = 0.003), an East Asian (n = 13 618; P = 6 × 10-4) and a South Asian (n = 7485; P = 0.025) genetic ancestry cohort, but not in a Hispanic/Latino cohort (n = 8726; P = 0.71). Furthermore, in a pan-ancestry (N = 483 235) meta-analysis of genome-wide association studies (GWAS) for habitual sleep duration, 73 loci are associated with genome-wide statistical significance. Follow-up of five loci (near HACD2, COG5, PRR12, SH3RF1 and KCNQ5) identified expression-quantitative trait loci for PRR12 and COG5 in brain tissues and pleiotropic associations with cardiovascular and neuropsychiatric traits. Overall, our results suggest that the genetic basis of sleep duration is at least partially shared across diverse ancestry groups.
无论是短期(每晚≤6 小时)还是长期(每晚≥9 小时)睡眠都会增加患慢性病的风险。尽管有证据表明习惯性睡眠时间与疾病风险有关,但人们对普通人群中睡眠持续时间的遗传决定因素知之甚少,尤其是在欧洲人群之外。在这里,我们报告称,78 个欧洲血统的睡眠持续时间单核苷酸多态性(SNP)的多基因评分与非洲人群(n=7288;P=0.003)、东亚人群(n=13618;P=6×10-4)和南亚人群(n=7485;P=0.025)的睡眠持续时间有关,但与西班牙裔/拉丁裔人群(n=8726;P=0.71)无关。此外,在一项针对习惯性睡眠时间的全基因组关联研究(GWAS)的泛血统(N=483235)荟萃分析中,有 73 个位点与全基因组统计显著性相关。对五个位点(靠近 HACD2、COG5、PRR12、SH3RF1 和 KCNQ5)的后续研究在脑组织中确定了 PRR12 和 COG5 的表达数量性状基因座,并与心血管和神经精神特征存在多效性关联。总的来说,我们的研究结果表明,睡眠持续时间的遗传基础至少在一定程度上是跨不同血统群体共享的。