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Title: Mendelian Randomisation study of the influence of eGFR on coronary heart disease
Authors: Charoen, Pimphen
Nitsch, Dorothea
Engmann, Jorgen
Shah, Tina
White, Jonathan
Zabaneh, Delilah
Jefferis, Barbara
Wannamethee, Goya
Whincup, Peter
Mulick Cassidy, Amy
Gaunt, Tom
Day, Ian
McLachlan, Stela
Price, Jacqueline
Kumari, Meena
Kivimaki, Mika
Brunner, Eric
Langenberg, Claudia
Ben-Shlomo, Yoav
Hingorani, Aroon
Whittaker, John
Pablo Casas, Juan
Dudbridge, Frank
UCLEB Consortium
First Published: 24-Jun-2016
Publisher: Nature Publishing Group
Citation: Scientific Reports, 2016, 6, Article number: 28514
Abstract: Impaired kidney function, as measured by reduced estimated glomerular filtration rate (eGFR), has been associated with increased risk of coronary heart disease (CHD) in observational studies, but it is unclear whether this association is causal or the result of confounding or reverse causation. In this study we applied Mendelian randomisation analysis using 17 genetic variants previously associated with eGFR to investigate the causal role of kidney function on CHD. We used 13,145 participants from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium and 194,427 participants from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus Coronary Artery Disease (CARDIoGRAMplusC4D) consortium. We observed significant association of an unweighted gene score with CHD risk (odds ratio = 0.983 per additional eGFR-increasing allele, 95% CI = 0.970-0.996, p = 0.008). However, using weights calculated from UCLEB, the gene score was not associated with disease risk (p = 0.11). These conflicting results could be explained by a single SNP, rs653178, which was not associated with eGFR in the UCLEB sample, but has known pleiotropic effects that prevent us from drawing a causal conclusion. The observational association between low eGFR and increased CHD risk was not explained by potential confounders, and there was no evidence of reverse causation, therefore leaving the remaining unexplained association as an open question.
DOI Link: 10.1038/srep28514
eISSN: 2045-2322
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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