Association between telomere length and hepatocellular carcinoma risk: A Mendelian randomization study

孟德尔随机化 全基因组关联研究 单核苷酸多态性 优势比 人口 遗传学 遗传关联 生物 置信区间 肿瘤科 医学 内科学 基因型 基因 环境卫生 遗传变异
作者
Chenglei Yang,Xi Wu,Siyu Chen,Bang‐De Xiang
出处
期刊:Cancer Medicine [Wiley]
卷期号:12 (8): 9937-9944 被引量:2
标识
DOI:10.1002/cam4.5702
摘要

Hepatocellular carcinoma (HCC) is a common cancer threatening the public health globally. Although HCC has been associated with the telomere length (TL), the causal relationship between them is not well understood. Therefore, we attempted to explore the linear causal relationship between TL and HCC through Mendelian randomization (MR) analysis among Asian and European populations.The summary statistics of TL-associated single nucleotide polymorphisms (SNPs) were obtained from a genome-wide association study (GWAS) in the Asian population (N = 23,096). The data of TL-associated SNPs in the European population (N = 472,174) and the GWAS summary statistics of HCC in the Asian population (1866 cases, 195,745 controls) as well as the European population (168 cases, 372,016 controls) were downloaded from the public GWAS database. Two-sample MR was performed using inverse variance weighting (IVW), weighted median estimate, MR-Egger regression, weighted-mode estimate, and simple-mode estimate methods. Sensitivity analysis was performed to text the primary results' robustness.Nine SNPs associated with TL in Asian populations and 98 SNPs in European populations were selected as instrumental variables. No linear causal relationship between heritable TL and the HCC risk was recorded in the Asian (IVW analysis odds ratio [OR] = 1.023, 95% confidence interval [CI] 0.745, 1.405, p = 0.887) and European populations (IVW analysis OR = 0.487, 95% CI 0.180, 1.320, p = 0.157). Other methods also achieved similar outcomes. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.No linear causal association was recorded between heritable TL and HCC in Asian and European populations.
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