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Polygenic risk scores for coronary artery disease and subsequent event risk amongst established cases

Howe, LJ; Dudbridge, F; Schmidt, AF; Finan, C; Denaxas, S; Asselbergs, FW; Hingorani, AD; (2020) Polygenic risk scores for coronary artery disease and subsequent event risk amongst established cases. Human Molecular Genetics 10.1093/hmg/ddaa052. (In press). Green open access

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Abstract

BACKGROUND: There is growing evidence that polygenic risk scores (PRS) can identify individuals with elevated lifetime risk of coronary artery disease (CAD). Whether they can also be used to stratify risk of subsequent events among those surviving a first CAD event remains uncertain, with possible biological differences between CAD onset and progression, and the potential for index event bias. METHODS: Using two baseline subsamples of UK Biobank; prevalent CAD cases (N = 10 287) and individuals without CAD (N = 393 108), we evaluated associations between a CAD PRS and incident cardiovascular and fatal outcomes. RESULTS: A 1 S.D. higher PRS was associated with increased risk of incident MI in participants without CAD (OR 1.33; 95% C.I. 1.29, 1.38), but the effect estimate was markedly attenuated in those with prevalent CAD (OR 1.15; 95% C.I. 1.06, 1.25); heterogeneity P = 0.0012. Additionally, among prevalent CAD cases, we found evidence of an inverse association between the CAD PRS and risk of all-cause death (OR 0.91; 95% C.I. 0.85, 0.98) compared to those without CAD (OR 1.01; 95% C.I. 0.99, 1.03); heterogeneity P = 0.0041. A similar inverse association was found for ischaemic stroke (Prevalent CAD (OR 0.78; 95% C.I. 0.67, 0.90); without CAD (OR 1.09; 95% C.I. 1.04, 1.15), heterogeneity P < 0.001). CONCLUSIONS: Bias induced by case stratification and survival into UK Biobank may distort associations of polygenic risk scores derived from case-control studies or populations initially free of disease. Differentiating between effects of possible biases and genuine biological heterogeneity is a major challenge in disease progression research.

Type: Article
Title: Polygenic risk scores for coronary artery disease and subsequent event risk amongst established cases
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/hmg/ddaa052
Publisher version: https://doi.org/10.1093/hmg/ddaa052
Language: English
Additional information: © The Author(s) 2020. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: coronary arteriosclerosisis, chemic stroke, heterogeneity, cardiovascular system, disease progression, fatal out come, survival, stratification, attenuation, lifetime risk, biobanks
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10094683
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