Riestra Pia, Gebreab Samson Y, Xu Ruihua, Khan Rumana J, Gaye Amadou, Correa Adolfo, Min Nancy, Sims Mario, Davis Sharon K
National Human Genome Research Institute Genomics of Metabolic, Cardiovascular and Inflammatory Disease Branch Social Epidemiology Research Unit, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA.
Jackson Heart Study, Jackson Medical Mall, 350 West Woodrow Wilson Av., Suite 701, Jackson, MS, 39217, USA.
BMC Genet. 2017 Jun 23;18(1):58. doi: 10.1186/s12863-017-0522-6.
Circadian rhythms regulate key biological processes and the dysregulation of the intrinsic clock mechanism affects sleep patterns and obesity onset. The CLOCK (circadian locomotor output cycles protein kaput) gene encodes a core transcription factor of the molecular circadian clock influencing diverse metabolic pathways, including glucose and lipid homeostasis. The primary objective of this study was to evaluate the associations between CLOCK single nucleotide polymorphisms (SNPs) and body mass index (BMI). We also evaluated the association of SNPs with BMI related factors such as sleep duration and quality, adiponectin and leptin, in 2962 participants (1116 men and 1810 women) from the Jackson Heart Study. Genotype data for the selected 23 CLOCK gene SNPS was obtained by imputation with IMPUTE2 software and reference phase data from the 1000 genome project. Genetic analyses were conducted with PLINK RESULTS: We found a significant association between the CLOCK SNP rs2070062 and sleep duration, participants carriers of the T allele showed significantly shorter sleep duration compared to non-carriers after the adjustment for individual proportions of European ancestry (PEA), socio economic status (SES), body mass index (BMI), alcohol consumption and smoking status that reach the significance threshold after multiple testing correction. In addition, we found nominal associations of the CLOCK SNP rs6853192 with longer sleep duration and the rs6820823, rs3792603 and rs11726609 with BMI. However, these associations did not reach the significance threshold after correction for multiple testing.
In this work, CLOCK gene variants were associated with sleep duration and BMI suggesting that the effects of these polymorphisms on circadian rhythmicity may affect sleep duration and body weight regulation in Africans Americans.
昼夜节律调节关键的生物过程，而内在时钟机制的失调会影响睡眠模式和肥胖的发生。生物钟（昼夜运动输出周期蛋白无功能）基因编码分子昼夜节律钟的一个核心转录因子，影响多种代谢途径，包括葡萄糖和脂质稳态。本研究的主要目的是评估生物钟单核苷酸多态性（SNP）与体重指数（BMI）之间的关联。我们还在来自杰克逊心脏研究的2962名参与者（1116名男性和1810名女性）中评估了SNP与BMI相关因素的关联，如睡眠时间和质量、脂联素和瘦素。通过使用IMPUTE2软件进行推算以及来自千人基因组计划的参考相位数据，获得了所选23个生物钟基因SNP的基因型数据。使用PLINK进行基因分析。结果：我们发现生物钟SNP rs2070062与睡眠时间之间存在显著关联，在对欧洲血统个体比例（PEA）、社会经济地位（SES）、体重指数（BMI）、饮酒和吸烟状况进行调整后，携带T等位基因的参与者与非携带者相比，睡眠时间显著缩短，在多重检验校正后达到显著阈值。此外，我们发现生物钟SNP rs6853192与较长睡眠时间存在名义上的关联，而rs6820823、rs3792603和rs11726609与BMI存在名义上的关联。然而，在多重检验校正后，这些关联未达到显著阈值。结论：在这项研究中，生物钟基因变异与睡眠时间和BMI相关，表明这些多态性对昼夜节律的影响可能会影响非裔美国人的睡眠时间和体重调节。
