Mendelian Randomisation study of the influence of eGFR on coronary heart disease

& the UCLEB Consortium, Pimphen Charoen, Dorothea Nitsch, Jorgen Engmann, Tina Shah, Jonathan White, Delilah Zabaneh, Barbara Jefferis, Goya Wannamethee, Peter Whincup, Amy Mulick Cassidy, Tom Gaunt, Ian Day, Stela Mclachlan, Jacqueline Price, Meena Kumari, Mika Kivimaki, Eric Brunner, Claudia Langenberg, Yoav Ben-shlomoAroon Hingorani, John Whittaker, Juan Pablo Casas, Frank Dudbridge

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 risk 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.
Original languageEnglish
Article number28514
JournalScientific Reports
Early online date24 Jun 2016
Publication statusE-pub ahead of print - 24 Jun 2016


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