한빛사논문
- 조회483
Sehoon Park MD1,2, Soojin Lee MD3, Yaerim Kim MD, PhD4, Semin Cho MD5, Kwangsoo KimPhD6, Yong Chul Kim MD, PhD5, Seung Seok Han MD, PhD5,8, Hajeong Lee MD, PhD5,8, Jung Pyo Lee MD, PhD7,8,9, Kwon Wook Joo MD, PhD5,7,8, Chun Soo Lim MD, PhD7,8,9, Yon Su Kim MD, PhD;1,5,7,8, Dong Ki Kim MD, PhD5,7,8,*
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
2Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do, Korea
3Division of Nephrology, Department of Internal Medicine, Uijeongbu Eulji University Medical Center
4Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
5Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
6Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea
7Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
8Kidney Research Institute, Seoul National University, Seoul, Korea
9Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
*Corresponding author.
Abstract
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.
논문정보
- Research article
- 2021년 07월 (BRIC 등록일 2021-08-23)
- 국내 연구진
- 의약학 > 응용의학
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