Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7LF, UK.
Nuffield Department of Population Health, BHF Centre of Research Excellence, University of Oxford, Oxford, OX3 7LF, UK.
Nat Commun. 2018 Dec 10;9(1):5257. doi: 10.1038/s41467-018-07743-4.
Physical activity and sleep duration are established risk factors for many diseases, but their aetiology is poorly understood, partly due to relying on self-reported evidence. Here we report a genome-wide association study (GWAS) of device-measured physical activity and sleep duration in 91,105 UK Biobank participants, finding 14 significant loci (7 novel). These loci account for 0.06% of activity and 0.39% of sleep duration variation. Genome-wide estimates of ~ 15% phenotypic variation indicate high polygenicity. Heritability is higher in women than men for overall activity (23 vs. 20%, p = 1.5 × 10) and sedentary behaviours (18 vs. 15%, p = 9.7 × 10). Heritability partitioning, enrichment and pathway analyses indicate the central nervous system plays a role in activity behaviours. Two-sample Mendelian randomisation suggests that increased activity might causally lower diastolic blood pressure (beta mmHg/SD: -0.91, SE = 0.18, p = 8.2 × 10), and odds of hypertension (Odds ratio/SD: 0.84, SE = 0.03, p = 4.9 × 10). Our results advocate the value of physical activity for reducing blood pressure.
身体活动和睡眠时长是许多疾病的既定风险因素，但它们的病因尚不清楚，部分原因是依赖于自我报告的证据。在这里，我们报告了一项针对 91105 名英国生物库参与者的设备测量身体活动和睡眠时长的全基因组关联研究（GWAS），发现了 14 个显著的位点（7 个是新的）。这些位点解释了身体活动和睡眠时长变异的 0.06%和 0.39%。全基因组估计约有 15%的表型变异表明其具有高度的多效性。女性的整体活动（23%比男性的 20%，p=1.5×10）和久坐行为（18%比男性的 15%，p=9.7×10）的遗传力都高于男性。遗传力划分、富集和通路分析表明中枢神经系统在活动行为中起作用。两样本孟德尔随机化表明，增加身体活动可能会导致舒张压降低（每标准差 β mmHg：-0.91，SE=0.18，p=8.2×10），以及高血压的几率降低（每标准差 OR：0.84，SE=0.03，p=4.9×10）。我们的研究结果表明，身体活动对于降低血压具有重要价值。
