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

ABSTRACT: BACKGROUND:There is growing evidence that polygenic risk scores (PRSs) can identify individuals with elevated lifetime risk of coronary artery disease (CAD). Whether they can also be used to stratify the risk of subsequent events among those surviving a first CAD event remain 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 SD higher PRS was associated with an increased risk of incident myocardial infarction (MI) in participants without CAD (OR 1.33; 95% CI 1.29, 1.38), but the effect estimate was markedly attenuated in those with prevalent CAD (OR 1.15; 95% CI 1.06, 1.25) and heterogeneity P?=?0.0012. Additionally, among prevalent CAD cases, we found an evidence of an inverse association between the CAD PRS and risk of all-cause death (OR 0.91; 95% CI 0.85, 0.98) compared with those without CAD (OR 1.01; 95% CI 0.99, 1.03) and heterogeneity P?=?0.0041. A similar inverse association was found for ischaemic stroke [prevalent CAD (OR 0.78; 95% CI 0.67, 0.90); without CAD (OR 1.09; 95% CI 1.04, 1.15), heterogeneity P?

SUBMITTER: Howe LJ

PROVIDER: S-EPMC7254844 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Howe Laurence J LJ Dudbridge Frank F Schmidt Amand F AF Finan Chris C Denaxas Spiros S Asselbergs Folkert W FW Hingorani Aroon D AD Patel Riyaz S RS

Human molecular genetics 20200501 8

<h4>Background</h4>There is growing evidence that polygenic risk scores (PRSs) can identify individuals with elevated lifetime risk of coronary artery disease (CAD). Whether they can also be used to stratify the risk of subsequent events among those surviving a first CAD event remain uncertain, with possible biological differences between CAD onset and progression, and the potential for index event bias.<h4>Methods</h4>Using two baseline subsamples of UK Biobank: prevalent CAD cases (N = 10 287) ...[more]

PMID: 32219344

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Project description:BackgroundEpidemiological studies have repeatedly observed a markedly higher risk for coronary artery disease (CAD) in Scotland as compared to England. Up to now, it is unclear whether environmental or genetic factors might explain this phenomenon.MethodsUsing UK Biobank (UKB) data, we assessed CAD risk, based on the Framingham risk score (FRS) and common genetic variants, to explore the respective contribution to CAD prevalence in Scotland (n = 31,963) and England (n = 317,889). We calculated FRS based on sex, age, body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), antihypertensive medication, smoking status, and diabetes. We determined the allele frequency of published genome-wide significant risk CAD alleles and a weighted genetic risk score (wGRS) for quantifying genetic CAD risk.ResultsPrevalence of CAD was 16% higher in Scotland as compared to England (8.98% vs. 7.68%, P < 0.001). However, the FRS only predicted a marginally higher CAD risk (less than 1%) in Scotland (12.5 ± 10.5 vs.12.6 ± 10.6, P = 0.03). Likewise, the overall number of genome-wide significant variants affecting CAD risk (157.6 ± 7.7 and 157.5 ± 7.7; P = 0.12) and a wGRS for CAD (2.49 ± 0.25 in both populations, P = 0.14) were remarkably similar in the English and Scottish population. Interestingly, we observed substantial differences in the allele frequencies of individual risk variants. Of the previously described 163 genome-wide significant variants studied here, 35 variants had higher frequencies in Scotland, whereas 37 had higher frequencies in England (P < 0.001 each).ConclusionsNeither the traditional risk factors included in the FRS nor a genetic risk score (GRS) based on established common risk alleles explained the higher CAD prevalence in Scotland. However, we observed marked differences in the distribution of individual risk alleles, which emphasizes that even geographically and ethnically closely related populations may display relevant differences in the genetic architecture of a common disease.

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

Publications

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

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