Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Nat Genet. 2013 Apr;45(4):422-7, 427e1-2. doi: 10.1038/ng.2528.
Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 × 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.
个体间白细胞端粒长度（LTL）的平均值存在差异，这种差异与癌症和几种与年龄相关的疾病有关。我们在此报告了一项针对 37684 人的全基因组荟萃分析，其中有 10739 人对选定的变体进行了复制。我们确定了七个与平均 LTL 相关的位点，包括五个新的位点（P<5×10(-8)）。这五个位点包含候选基因（TERC、TERT、NAF1、OBFC1 和 RTEL1），这些基因已知与端粒生物学有关。两个位点（TERC 和 TERT）的主要 SNP 与几种癌症和其他疾病相关，包括特发性肺纤维化。此外，对 22233 例冠心病病例和 64762 例对照中所有 7 个位点的主要变异进行的遗传风险评分分析显示，与较短 LTL 相关的等位基因与冠心病风险增加相关（LTL 每标准偏差增加 21%（95%置信区间，5-35%），P=0.014）。我们的研究结果支持端粒长度变异在某些与年龄相关的疾病中具有因果关系。
