The causal effects of serum lipids and apolipoproteins on kidney function: multivariable and bidirectional Mendelian-randomization analyses
Year: 2021
Type: article
Study design: Observational Study
Abstract: 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.
DOI: 10.1093/ije/dyab014
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
Institutions: University of Engineering and Technology Lahore, Norwegian University of Science and Technology, University of Bristol, MRC Integrative Epidemiology Unit, University of Cambridge, Levanger Hospital, Helse Nord-Trøndelag HF, St Olav's University Hospital, University of Michigan, MRC Biostatistics Unit, NIHR Bristol Biomedical Research Centre
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,413
Funders: Norges Teknisk-Naturvitenskapelige Universitet, Wellcome Trust, University Hospitals Bristol NHS Foundation Trust, National Institute for Health and Care Research, British Heart Foundation, Academy of Medical Sciences, University of Bristol, Helse Midt-Norge, Fakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige Universitet, Medical Research Council, Faculty of Medicine and Health, University of Sydney, Norwegian Institute of Public Health
Awards: Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, NIHR Senior Investigator Award, G2291477964, Large-scale integrative genomic studies of high-dimensional traits in cardiovascular diseases (renewal), G3414120251, G4122502716, G5850737185, The BHF Chair of Epidemiology and Medicine, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application (renewal). (Joint funding with MRC), G7881077065, G7990456425
OpenAlex ID: W3133712002