Pleiotropic genetic architecture and novel loci for C-reactive protein levels

Fotios Koskeridis (), Evangelos Evangelou, Saredo Said, Joseph J. Boyle, Paul Elliott, Abbas Dehghan and Ioanna Tzoulaki
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Fotios Koskeridis: University of Ioannina Medical School
Evangelos Evangelou: University of Ioannina Medical School
Saredo Said: University of Oxford
Joseph J. Boyle: Imperial College London
Paul Elliott: Imperial College London
Abbas Dehghan: Imperial College London
Ioanna Tzoulaki: University of Ioannina Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract C-reactive protein is involved in a plethora of pathophysiological conditions. Many genetic loci associated with C-reactive protein are annotated to lipid and glucose metabolism genes supporting common biological pathways between inflammation and metabolic traits. To identify novel pleiotropic loci, we perform multi-trait analysis of genome-wide association studies on C-reactive protein levels along with cardiometabolic traits, followed by a series of in silico analyses including colocalization, phenome-wide association studies and Mendelian randomization. We find 41 novel loci and 19 gene sets associated with C-reactive protein with various pleiotropic effects. Additionally, 41 variants colocalize between C-reactive protein and cardiometabolic risk factors and 12 of them display unexpected discordant effects between the shared traits which are translated into discordant associations with clinical outcomes in subsequent phenome-wide association studies. Our findings provide insights into shared mechanisms underlying inflammation and lipid metabolism, representing potential preventive and therapeutic targets.

Date: 2022
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DOI: 10.1038/s41467-022-34688-6

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