The causal effects of serum lipids and apolipoproteins on kidney function: multivariable and bidirectional Mendelian-randomization analyses
| Autor: | Ole-Jørgen Bekkevold, Stein Hallan, Jie Zheng, George Davey Smith, Solfrid Romundstad, Maiken Elvestad Gabrielsen, Bjørn Olav Åsvold, Ben Michael Brumpton, Humaira Rasheed, Kristian Hveem, Laurent F. Thomas, Jessica M. B. Rees, Tom G. Richardson, Si Fang, Tom R. Gaunt, Eleanor Sanderson, Anne Heidi Skogholt, Cristen J. Willer, Stephen Burgess, Endre Bakken Stovner |
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| Přispěvatelé: | Rees, Jessica [0000-0002-1495-2470], Sanderson, Eleanor [0000-0001-5188-5775], Richardson, Tom G [0000-0002-7918-2040], Brumpton, Ben [0000-0002-3058-1059], Burgess, Stephen [0000-0001-5365-8760], Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty kidney Apolipoprotein B Epidemiology Blood lipids Renal function 030204 cardiovascular system & hematology lipids 03 medical and health sciences chemistry.chemical_compound Random Allocation 0302 clinical medicine Internal medicine urinary albumin-to-creatinine ratio Mendelian randomization medicine eGFR Humans AcademicSubjects/MED00860 Triglycerides urinary albumen to creatinine ratio Creatinine biology Triglyceride business.industry Mendelian Randomization Analysis General Medicine Lipids 030104 developmental biology Endocrinology Apolipoproteins chemistry Cystatin C biology.protein lipids (amino acids peptides and proteins) business apolipoproteins Genome-Wide Association Study |
| Zdroj: | Rasheed, H, Zheng, J, Rees, J, Sanderson, E, Thomas, L, Richardson, T G, Fang, S, Bekkevold, O-J, Stovner, E B, Gabrielsen, M E, Skogholt, A H, Romundstad, S, Brumpton, B, Hallan, S, Willer, C, Burgess, S, Hveem, K, Davey Smith, G, Gaunt, T R & Asvold, B O 2021, ' The causal effects of serum lipids and apolipoproteins on kidney function : multivariable and bidirectional Mendelian randomization analyses ', International Journal of Epidemiology, vol. 50, no. 5, pp. 1569-1579 . https://doi.org/10.1093/ije/dyab014 International Journal of Epidemiology |
| DOI: | 10.1093/ije/dyab014 |
| Popis: | Background The causal nature of the observed associations between serum lipids and apolipoproteins and kidney function are unclear. Methods Using two-sample and multivariable Mendelian randomization (MR), we examined the causal effects of serum lipids and apolipoproteins on kidney function, indicated by the glomerular-filtration rate estimated using creatinine (eGFRcrea) or cystatin C (eGFRcys) and the urinary albumin-to-creatinine ratio (UACR). We obtained lipid- and apolipoprotein-associated genetic variants from the Global Lipids Genetics Consortium (n = 331 368) and UK Biobank (n = 441 016), respectively, and kidney-function markers from the Trøndelag Health Study (HUNT; n = 69 736) and UK Biobank (n = 464 207). The reverse causal direction was examined using variants associated with kidney-function markers selected from recent genome-wide association studies. Results There were no strong associations between genetically predicted lipid and apolipoprotein levels with kidney-function markers. Some, but inconsistent, evidence suggested a weak association of higher genetically predicted atherogenic lipid levels [indicated by low-density lipoprotein cholesterol (LDL-C), triglycerides and apolipoprotein B] with increased eGFR and UACR. For high-density lipoprotein cholesterol (HDL-C), results differed between eGFRcrea and eGFRcys, but neither analysis suggested substantial effects. We found no clear evidence of a reverse causal effect of eGFR on lipid or apolipoprotein traits, but higher UACR was associated with higher LDL-C, triglyceride and apolipoprotein B levels. Conclusion Our MR estimates suggest that serum lipid and apolipoprotein levels do not cause substantial changes in kidney function. A possible weak effect of higher atherogenic lipids on increased eGFR and UACR warrants further investigation. Processes leading to higher UACR may lead to more atherogenic lipid levels. |
| Databáze: | OpenAIRE |
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