Polygenic risk score and coronary artery disease: A meta-analysis of 979,286 participant data.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Ireland NLM ID: 0242543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1484 (Electronic) Linking ISSN: 00219150 NLM ISO Abbreviation: Atherosclerosis Subsets: MEDLINE
    • Publication Information:
      Publication: Limerick : Elsevier
      Original Publication: Amsterdam, Elsevier.
    • Subject Terms:
      Coronary Artery Disease*/genetics; Genetic Predisposition to Disease ; Humans ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide ; Prospective Studies ; Risk Factors
    • Abstract:
      Background and Aims: Coronary artery disease (CAD) is a complex disease with a strong genetic basis. While previous studies have combined common single-nucleotide polymorphisms (SNPs) into a polygenic risk score (PRS) to predict CAD risk, this association is poorly characterised. We performed a meta-analysis to estimate the effect of PRS on the risk of CAD.
      Methods: Online databases were searched for studies reporting PRS and CAD. PRS computation was based on log-odds (PRS LN ), pruning or clumping and thresholding (PRS P/C + T ), Lassosum regression (PRS Lassosum ), LDpred (PRS LDpred ), or metaGRS (PRS metaGRS ). The reported odds ratio (OR), hazard ratio (HR), C-indexes and their corresponding 95% confidence interval (95% CI) were pooled in a random-effects meta-analysis.
      Results: Forty-nine studies were included (979,286 individuals). There was a significant association between 1-standard deviation [SD] increment in PRS and adjusted risks of both incident and prevalent CAD (OR [95% CI]: 1.67 [1.57-1.77] for PRS metaGRS , 1.46 [1.26-1.68] for PRS LDpred ). The risk of incident CAD was highest for PRS P/C + T (HR [95% CI]: 1.49 [1.26-1.78]), PRS metaGRS (1.37 [1.27-1.47]), and PRS LDpred (1.36 [1.31-1.42]). Analysis of model performance demonstrated that PRS predicted incident CAD with C-index of up to 0.71. Importantly, addition of PRS to clinical risk scores resulted in modest but statistically significant improvements in CAD risk prediction, with 1.5% observed for PRS P/C + T (p < 0.001) and 1.6% for PRS LDpred (p < 0.001).
      Conclusions: Polygenic risk score is strongly associated with increased risks of CAD. Future prospective studies should explore the usefulness of polygenic risk scores for identifying individuals at a high risk of developing CAD.
      (Copyright © 2021 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Coronary artery disease; Genome-wide association study; Myocardial infarction; Polygenic risk score; Single-nucleotide polymorphism
    • Publication Date:
      Date Created: 20210823 Date Completed: 20211026 Latest Revision: 20211026
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.atherosclerosis.2021.08.020
    • Accession Number:
      34425527