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The influence of rare variants in circulating metabolic biomarkers

Author

Listed:
  • Fernando Riveros-Mckay
  • Clare Oliver-Williams
  • Savita Karthikeyan
  • Klaudia Walter
  • Kousik Kundu
  • Willem H Ouwehand
  • David Roberts
  • Emanuele Di Angelantonio
  • Nicole Soranzo
  • John Danesh
  • INTERVAL Study
  • Eleanor Wheeler
  • Eleftheria Zeggini
  • Adam S Butterworth
  • Inês Barroso

Abstract

Circulating metabolite levels are biomarkers for cardiovascular disease (CVD). Here we studied, association of rare variants and 226 serum lipoproteins, lipids and amino acids in 7,142 (discovery plus follow-up) healthy participants. We leveraged the information from multiple metabolite measurements on the same participants to improve discovery in rare variant association analyses for gene-based and gene-set tests by incorporating correlated metabolites as covariates in the validation stage. Gene-based analysis corrected for the effective number of tests performed, confirmed established associations at APOB, APOC3, PAH, HAL and PCSK (p

Suggested Citation

  • Fernando Riveros-Mckay & Clare Oliver-Williams & Savita Karthikeyan & Klaudia Walter & Kousik Kundu & Willem H Ouwehand & David Roberts & Emanuele Di Angelantonio & Nicole Soranzo & John Danesh & INTE, 2020. "The influence of rare variants in circulating metabolic biomarkers," PLOS Genetics, Public Library of Science, vol. 16(3), pages 1-19, March.
    • Handle: RePEc:plo:pgen00:1008605
    DOI: 10.1371/journal.pgen.1008605
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    1. Eugene P. Rhee & Qiong Yang & Bing Yu & Xuan Liu & Susan Cheng & Amy Deik & Kerry A. Pierce & Kevin Bullock & Jennifer E. Ho & Daniel Levy & Jose C. Florez & Sek Kathiresan & Martin G. Larson & Ramach, 2016. "An exome array study of the plasma metabolome," Nature Communications, Nature, vol. 7(1), pages 1-7, November.
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