The causal effects of serum lipids and apolipoproteins on kidney function: multivariable and bidirectional Mendelian-randomization analyses.
Stovner, Endre Bakken
Gabrielsen, Maiken Elvestad
Skogholt, Anne Heidi
Davey Smith, George
Gaunt, Tom R
Åsvold, Bjørn Olav
International journal of epidemiology
Oxford University Press (OUP)
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Rasheed, H., Zheng, J., Rees, J., Sanderson, E., Thomas, L., Richardson, T. G., Fang, S., et al. (2021). The causal effects of serum lipids and apolipoproteins on kidney function: multivariable and bidirectional Mendelian-randomization analyses.. International journal of epidemiology https://doi.org/10.1093/ije/dyab014
Background: The causal nature of the observed associations between serum lipids and kidney function is unclear. Subjects and Methods: Using two-sample and multivariable Mendelian randomization (MR), we examined the causal effects of serum lipids and apolipoproteins on kidney function, indicated by glomerular filtration rate estimated using creatinine (eGFRcrea) or cystatin C (eGFRcys), and 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 GWASs. Results: There was some, but inconsistent evidence that higher genetically predicted levels of atherogenic lipids indicated by LDL cholesterol, triglycerides and Apolipoprotein B were associated with modestly increased eGFR and UACR. For HDL cholesterol, results differed between eGFRcrea and eGFRcys, and between univariable and multivariable MR, but neither analysis suggested substantial effects. We found no clear evidence of a reverse causal effect of eGFR on lipid or apolipoprotein traits, but genetically predicted higher UACR was associated with higher LDL cholesterol, triglyceride and apolipoprotein B levels. Conclusion: Our MR estimates suggest that serum lipid and apolipoproteins levels do not cause substantial changes in kidney function, but higher atherogenic lipid levels may modestly increase glomerular filtration and UACR. There was no consistent evidence that eGFR may influence serum lipid or apolipoproteins levels, but genetically predicted higher UACR may lead to more atherogenic lipids.
Dr. Zhang is supported by the Vice-Chancellor fellowship and Dr. Sanderson is supported by Medical Research Council (MC_UU_00011/1) during the study. Dr. Gaunt received grants from UK Medical Research Council (MC_UU_00011/4), and GlaxoSmithKline, grants from Biogen.
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External DOI: https://doi.org/10.1093/ije/dyab014
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317769
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