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

Area of Science:

• Nephrology
• Cardiology
• Genetics

Background:

• Observational studies link impaired kidney function (reduced estimated glomerular filtration rate, eGFR) to increased coronary heart disease (CHD) risk.
• The causal nature of this association remains uncertain due to potential confounding factors and reverse causation.

Purpose of the Study:

• To investigate the causal role of kidney function on coronary heart disease (CHD) using Mendelian randomization analysis.
• To clarify whether reduced eGFR is a causal risk factor for CHD.

Main Methods:

• Mendelian randomization analysis was employed using 17 genetic variants associated with eGFR.
• Data from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium (13,145 participants) and the CARDIoGRAMplusC4D consortium (194,427 participants) were utilized.
• Both unweighted and weighted gene scores were analyzed for association with CHD risk.

Main Results:

• An unweighted gene score showed a significant association with increased CHD risk (OR=0.983 per eGFR-increasing allele, P=0.008).
• However, using weights derived from the UCLEB sample, the gene score was not significantly associated with CHD risk (P=0.11).
• A single nucleotide polymorphism (SNP), rs653178, with known pleiotropic effects, may explain the conflicting results, preventing a definitive causal conclusion.

Conclusions:

• The study did not establish a causal link between impaired kidney function and coronary heart disease using Mendelian randomization.
• The observational association between reduced eGFR and increased CHD risk persists as an open question, as confounding and reverse causation were not identified as explanations.