孟德尔随机化
肾脏疾病
医学
肾功能
优势比
生命银行
置信区间
内科学
端粒
遗传学
人口
生物
基因型
基因
环境卫生
遗传变异
作者
Sehoon Park,Soo Jin Lee,Yaerim Kim,Semin Cho,Kwangsoo Kim,Yong Chul Kim,Seung Seok Han,Hajeong Lee,Jung Pyo Lee,Kwon Wook Joo,Chun Soo Lim,Yon Su Kim,Yon Su Kim
标识
DOI:10.1016/j.kint.2021.06.041
摘要
Chronic kidney disease (CKD) is highly prevalent in the elderly population. However, it is rarely investigated whether kidney function is causally linked to biological aging itself. In this Mendelian randomization study, genetic instruments for telomere attrition were applied to a CKDGen genome wide association study results for 41,395 cases of CKD among 480,698 individuals as summary-level Mendelian randomization. A replicative analysis was performed by polygenic score analysis using independent United Kingdom Biobank data for 8,118 cases of CKD among 321,024 white individuals of British ancestry. Reverse-direction Mendelian randomization analysis was performed utilizing genetic instruments for log-estimated glomerular filtration rate change with Z-standardized telomere length outcome data for 326,075 participants in the UK Biobank. Genetic predisposition toward telomere attrition (one Z score decrease in length) was found to be a causative factor for a higher CKD risk [Odds Ratio 1.20 (95% confidence interval 1.08‒1.33)], as supported by pleiotropy-robust Mendelian randomization sensitivity analyses implemented using the CKDGen data. Based on United Kingdom Biobank data, the polygenic score for telomere attrition was significantly associated with a higher risk of CKD [1.20 (1.04‒1.39)]. In reverse-direction Mendelian randomization, the genetically predicted kidney function decrease was significantly associated with a higher degree of telomere attrition [beta 0.039 (0.009‒0.069)]. Thus, our study supports the causal linkage between telomere attrition and kidney function impairment.
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