Charoen, P and Nitsch, D and Engmann, J and Shah, T and White, J and Zabaneh, D and Jefferis, B and Wannamethee, G and Whincup, P and Mulick Cassidy, A and Gaunt, T and Day, I and McLachlan, S and Price, J and Kumari, M and Kivimaki, M and Brunner, E and Langenberg, C and Ben-Shlomo, Y and Hingorani, A and Whittaker, J and Pablo Casas, J and Dudbridge, F and Dale, C and Finan, C and Wong, A and Ong, K and Drenos, F and Cooper, J and Sofat, R and Schmidt, F and Lawlor, DA and Talmud, PJ and Humphries, SE and Hardy, R and Kuh, D and Wareham, N and Morris, R and Plagno, V (2016) Mendelian Randomisation study of the influence of eGFR on coronary heart disease. Scientific Reports, 6 (1). 28514-. DOI https://doi.org/10.1038/srep28514
Charoen, P and Nitsch, D and Engmann, J and Shah, T and White, J and Zabaneh, D and Jefferis, B and Wannamethee, G and Whincup, P and Mulick Cassidy, A and Gaunt, T and Day, I and McLachlan, S and Price, J and Kumari, M and Kivimaki, M and Brunner, E and Langenberg, C and Ben-Shlomo, Y and Hingorani, A and Whittaker, J and Pablo Casas, J and Dudbridge, F and Dale, C and Finan, C and Wong, A and Ong, K and Drenos, F and Cooper, J and Sofat, R and Schmidt, F and Lawlor, DA and Talmud, PJ and Humphries, SE and Hardy, R and Kuh, D and Wareham, N and Morris, R and Plagno, V (2016) Mendelian Randomisation study of the influence of eGFR on coronary heart disease. Scientific Reports, 6 (1). 28514-. DOI https://doi.org/10.1038/srep28514
Charoen, P and Nitsch, D and Engmann, J and Shah, T and White, J and Zabaneh, D and Jefferis, B and Wannamethee, G and Whincup, P and Mulick Cassidy, A and Gaunt, T and Day, I and McLachlan, S and Price, J and Kumari, M and Kivimaki, M and Brunner, E and Langenberg, C and Ben-Shlomo, Y and Hingorani, A and Whittaker, J and Pablo Casas, J and Dudbridge, F and Dale, C and Finan, C and Wong, A and Ong, K and Drenos, F and Cooper, J and Sofat, R and Schmidt, F and Lawlor, DA and Talmud, PJ and Humphries, SE and Hardy, R and Kuh, D and Wareham, N and Morris, R and Plagno, V (2016) Mendelian Randomisation study of the influence of eGFR on coronary heart disease. Scientific Reports, 6 (1). 28514-. DOI https://doi.org/10.1038/srep28514
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.
Item Type: | Article |
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Uncontrolled Keywords: | UCLEB Consortium; Kidney; Humans; Coronary Disease; Glomerular Filtration Rate; Odds Ratio; Risk Factors; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Mendelian Randomization Analysis |
Subjects: | H Social Sciences > H Social Sciences (General) R Medicine > R Medicine (General) |
Divisions: | Faculty of Social Sciences Faculty of Social Sciences > Institute for Social and Economic Research |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 14 Feb 2017 12:43 |
Last Modified: | 07 Aug 2024 19:49 |
URI: | http://repository.essex.ac.uk/id/eprint/18504 |
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Licence: Creative Commons: Attribution 3.0
Filename: srep28514-s1.doc