| Title: | The causal effects of serum lipids and apolipoproteins on kidney function: multivariable and bidirectional Mendelian-randomization analyses |
| Journal: | International Journal of Epidemiology |
| Published: | 21 Jun 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34151951/ |
| DOI: | https://doi.org/10.1093/ije/dyab014 |
Publication 5826
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Abstract
BACKGROUND: The causal nature of the observed associations between serum lipids and apolipoproteins and kidney function are unclear.</p>
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.</p>
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.</p>
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.</p>
8 Keywords
- Apolipoproteins
- Genome-Wide Association Study
- Humans
- Kidney
- Lipids
- Mendelian Randomization Analysis
- Random Allocation
- Triglycerides
20 Authors
- Humaira Rasheed
- Jie Zheng
- Jessica Rees
- Eleanor Sanderson
- Laurent Thomas
- Tom G Richardson
- Si Fang
- Ole-Jørgen Bekkevold
- Endre Bakken Stovner
- Maiken Elvestad Gabrielsen
- Anne Heidi Skogholt
- Solfrid Romundstad
- Ben Brumpton
- Stein Hallan
- Cristen Willer
- Stephen Burgess
- Kristian Hveem
- George Davey Smith
- Tom R Gaunt
- Bjørn Olav Åsvold
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