Understanding the relationship between circulating lipids and risk of chronic kidney disease: a prospective cohort study and large-scale genetic analyses

作者：Yutong Wang, Li Zhang, Wenqiang Zhang, Mingshuang Tang, Huijie Cui, Xueyao Wu, Xunying Zhao, Lin Chen, Peijing Yan, Chao Yang, Chenghan Xiao, Yanqiu Zou, Yunjie Liu, Ling Zhang, Chunxia Yang, Yuqin Yao, Jiayuan Li, Zhenmi Liu, Xia Jiang, Ben Zhang · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04509-5 · 被引用次数：16 · 研究领域：Chronic Kidney Disease and Diabetes、Diabetes, Cardiovascular Risks, and Lipoproteins、Genetic Associations and Epidemiology

Abstract Background This study aims to comprehensively investigate the phenotypic and genetic relationships between four common lipids (high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; total cholesterol, TC; and triglycerides, TG), chronic kidney disease (CKD), and estimated glomerular filtration rate (eGFR). Methods We first investigated the observational association of lipids (exposures) with CKD (primary outcome) and eGFR (secondary outcome) using data from UK Biobank. We then explored the genetic relationship using summary statistics from the largest genome-wide association study of four lipids (N = 1,320,016), CKD (N case = 41,395, N control = 439,303), and eGFR(N = 567,460). Results There were significant phenotypic associations (HDL-C: hazard ratio (HR) = 0.76, 95%CI = 0.60–0.95; TG: HR = 1.08, 95%CI = 1.02–1.13) and global genetic correlations (HDL-C: $${r}_{g}$$ r g = − 0.132, P = 1.00 × 10 –4 ; TG: $${r}_{g}$$ r g = 0.176; P = 2.66 × 10 –5 ) between HDL-C, TG, and CKD risk. Partitioning the whole genome into 2353 LD-independent regions, twelve significant regions were observed for four lipids and CKD. The shared genetic basis was largely explained by 29 pleiotropic loci and 36 shared gene-tissue pairs. Mendelian randomization revealed an independent causal relationship of genetically predicted HDL-C (odds ratio = 0.91, 95%CI = 0.85–0.98), but not for LDL-C, TC, or TG, with the risk of CKD. Regarding eGF...