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Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

Jon White1, Reecha Sofat2, Gibran Hemani3

  • 1UCL Genetics Institute, University College, London, UK.

The Lancet. Diabetes & Endocrinology
|January 20, 2016
PubMed

Insights

High plasma urate levels are linked to coronary heart disease risk. Mendelian randomization analyses suggest a potential causal role for urate, but further investigation is needed to confirm this link.

Area of Science:

  • Cardiovascular Disease Epidemiology
  • Genetic Epidemiology
  • Metabolic Health

Background:

  • Elevated plasma urate concentration is associated with increased coronary heart disease (CHD) risk.
  • The causal relationship between urate and CHD remains uncertain.

Purpose of the Study:

  • To investigate the causal role of plasma urate in the development of coronary heart disease using Mendelian randomization (MR).

Main Methods:

  • Performed a meta-analysis of observational studies on urate and CHD risk.
  • Utilized conventional, multivariable, and Egger Mendelian randomization analyses with 31 urate-associated SNPs.
  • Accounted for potential pleiotropy through multivariable and MR-Egger approaches.

Main Results:

  • Observational meta-analysis showed a 1.07 odds ratio (OR) for CHD per 1 SD increase in urate.
  • Conventional MR yielded an OR of 1.18, multivariable MR an OR of 1.10, and MR-Egger an OR of 1.05 per 1 SD urate increase.
  • Estimates varied, with MR-Egger suggesting a potentially null causal effect due to accounting for pleiotropy.

Conclusions:

  • Mendelian randomization analyses suggest a causal link between urate and coronary heart disease development.
  • Potential pleiotropy may inflate conventional and multivariate MR estimates.
  • MR-Egger analysis, while less powerful, indicates a possible lack of a causal effect, warranting further research to prioritize urate-lowering interventions.
Abstract

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