Incremental value of a genetic risk score for the prediction of new vascular events in patients with clinically manifest vascular disease

Weijmans, Maaike; Bakker, Paul I. W. de; Graaf, Yolanda van der; Asselbergs, Folkert W.; Algra, Ale; Borst, Gert J. de; Spiering, Wilko; Visseren, Frank L.J.

doi:10.1016/j.atherosclerosis.2015.02.008

Cited by 34 publications

(27 citation statements)

References 29 publications

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“…As more genetic data becomes readily available researchers are using GRS in different ways. This includes assessing heritability [Chatterjee et al, 2013;Purcell et al, 2009], Mendelian randomization studies [Palmer et al, 2012], and risk prediction [Weijmans et al, 2015]. Having a means to optimally develop a GRS within a specific research context is important.…”

Section: Discussionmentioning

confidence: 99%

Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach

Goldstein

Salfati

Assimes

2015

Genetic Epidemiology

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Genetic Risk Scores are an increasingly popular tool for summarizing the cumulative risk of a set of SNPs with disease. Typically only the set of the SNPs that have reached genome-wide significance compose these scores. However recent work suggests that including additional SNPs may aid risk assessment. In this paper, we used the Atherosclerosis Risk in Communities Study (ARIC) cohort to illustrate how one can choose the optimal set of SNPs for a GRS. In addition to p-value threshold, we also examined linkage disequilibrium, imputation quality and imputation type. We provide a variety of evaluation metrics. Results suggest that p-value threshold had the greatest impact on GRS quality for the outcome of coronary heart disease, with an optimal threshold around 0.001. However, GRSs are relatively robust to both linkage disequilibrium and imputation quality. We also show that the optimal GRS partially depends on the evaluation metric and consequently the way one intends to use the GRS. Overall the implications highlight both the robustness of GRS and a means to empirically choose the best set of GRSs.

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Section: Discussionmentioning

confidence: 99%

Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach

Goldstein

Salfati

Assimes

2015

Genetic Epidemiology

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“…Importantly, a subsequent analysis of the same patient cohort used by Tagrante et al showed that the GRS did not improve predictive capacity above and beyond the SMART risk score, in patients with established vascular disease. 37 …”

Section: Discussionmentioning

confidence: 99%

Utility of a genetic risk score to predict recurrent cardiovascular events 1 year after an acute coronary syndrome: A pooled analysis of the RISCA, PRAXY, and TRIUMPH cohorts

et al. 2015

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Background Limited evidence exists regarding the utility of genetic risk scores (GRS) in predicting recurrent cardiovascular events after acute coronary syndrome (ACS). We sought to determine whether a GRS would predict early recurrent cardiovascular events within 1 year of ACS. Methods & Results Participants admitted with acute coronary syndromes from the RISCA, PRAXY, and TRIUMPH cohorts, were genotyped for 30 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) or myocardial infarction (MI) in prior genome wide association studies. A 30 SNP CAD/MI GRS was constructed. The primary endpoint was defined as all-cause mortality, recurrent ACS or cardiac re-hospitalization within 1 year of ACS admission. Results across all cohorts for the 30 SNP CAD/MI GRS were pooled using a random-effects model. There were 1040 patients from the RISCA cohort, 691 patients from the PRAXY cohort, and 1772 patients from the TRIUMPH cohort included in the analysis and 389 occurrences of the primary endpoint of recurrent events at 1-year post-ACS. In unadjusted and fully adjusted analyses, a 30 SNP GRS was not significantly associated with recurrent events (HR per allele 0.97 (95%CI 0.91–1.03) for RISCA, HR 0.99 (95%CI 0.93–1.05) for PRAXY, 0.98 (95%CI 0.94–1.02) for TRIUMPH, and 0.98 (95%CI 0.95–1.01) for the pooled analysis). Addition of this GRS to the GRACE risk model did not significantly improve risk prediction. Conclusion The 30 MI SNP GRS was not associated with recurrent events 1-year post ACS in pooled analyses across cohorts and did not improve risk discrimination or reclassification indices. Our results suggest that the genetic etiology of early events post-ACS may differ from later events.

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“…Initial risk scores based on 13 SNPs showed significant association with CVD but no substantial improvement in risk prediction. [46][47][48][49] More recent studies based on ≤50 SNPs showed similar significant relationships for incident disease and suggest that the prediction improves as more SNPs are incorporated [50][51][52][53][54][55] Two studies examining 28 SNPs 54 and 50 SNPs 55 showed improvements in prediction which were independent of family history (Figure 1).…”

Section: Genetic Markers Of Riskmentioning

confidence: 88%

Are Genetic Tests for Atherosclerosis Ready for Routine Clinical Use?

Paynter

Ridker

Chasman

2016

Circulation Research

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T he Presidential Precision Medicine Initiative imagines a future in which medical decisions are increasingly tailored to the clinical profile of each patient.1 Incorporation of genetic information is a key component of the envisioned profile, continuing the goals of integration with patient care set out at the completion of the human genome sequence 15 years ago. As the cost of determining genetic information plummets and point-of-care genetic analysis is increasingly available, it Atherosclerosis Compendium© 2016 American Heart Association, Inc.

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Incremental value of a genetic risk score for the prediction of new vascular events in patients with clinically manifest vascular disease

Cited by 34 publications

References 29 publications

Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach

Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach

Utility of a genetic risk score to predict recurrent cardiovascular events 1 year after an acute coronary syndrome: A pooled analysis of the RISCA, PRAXY, and TRIUMPH cohorts

Are Genetic Tests for Atherosclerosis Ready for Routine Clinical Use?

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