| Title: | Understanding the relationship between circulating lipids and risk of chronic kidney disease: a prospective cohort study and large-scale genetic analyses |
| Journal: | Journal of Translational Medicine |
| Published: | 27 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37759214/ |
| DOI: | https://doi.org/10.1186/s12967-023-04509-5 |
| URL: | https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-023-04509-5 |
Publication 9462
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Abstract
BackgroundThis 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).MethodsWe 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 (Ncase = 41,395, Ncontrol = 439,303), and eGFR(N = 567,460).ResultsThere 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: rg$${r}_{g}$$ = − 0.132, P = 1.00 × 10-4; TG: rg$${r}_{g}$$ = 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 eGFR, a similar pattern of correlation and pleiotropy was observed.ConclusionsOur work demonstrates a putative causal role of HDL-C in CKD and a significant biological pleiotropy underlying lipids and CKD in populations of European ancestry. Management of low HDL-C levels could potentially benefit in reducing the long-term risk of CKD.Graphical Abstract</p>
20 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 50538 | Relationships between blood, urinary and other biomarkers and risk of human noncommunicable diseases, all-cause mortality, and cause-specific mortality |
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