Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

Wang, Minxian; Menon, Ramesh; Mishra, Sanghamitra; Patel, Aniruddh P.; Chaffin, Mark; Tanneeru, Deepak; Deshmukh, Manjari; Mathew, Oshin; Apte, Sanika; Devanboo, Christina S.; Sundaram, Sumathi; Lakshmipathy, Praveena; Murugan, Sakthivel; Sharma, Krishna Kumar; Rajendran, Karthikeyan; Santhosh, Sam; Thachathodiyl, Rajesh; Ahamed, Hisham; Balegadde, Aniketh Vijay; Alexander, Tobias; Swaminathan, Krishnan; Gupta, Rajeev; Mullasari, Ajit S.; Sigamani, Alben; Kanchi, Muralidhar; Peterson, Andrew S.; Butterworth, Adam S.; Danesh, John; Angelantonio, Emanuele Di; Naheed, Aliya; Inouye, Michael; Chowdhury, Rajiv; Vedam, Ramprasad; Kathiresan, Sekar; Gupta, Ravi; Khera, Amit

doi:10.1016/j.jacc.2020.06.024

Cited by 83 publications

(72 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are risk variants specific for ethnic groups, which can be imputed onto existing microarrays, as recently shown by Wang et al. ( 139 ) for South Asians.…”

Section: A Future Prospectivementioning

confidence: 99%

Genetic Risk Stratification

Roberts

Chang

Hadley

2021

JACC: Basic to Translational Science

View full text Add to dashboard Cite

Highlights CAD is a pandemic that can be prevented. Conventional risk factors are inadequate to detect who is at risk early in the asymptomatic stage. Genetic risk for CAD can be determined at birth, and those at highest genetic risk have been shown to respond to lifestyle changes and statin therapy with a 40% to 50% reduction in cardiac events. Genetic risk stratification for CAD should be brought to the bedside in an attempt to prevent this pandemic disease.

show abstract

“…There are risk variants specific for ethnic groups, which can be imputed onto existing microarrays, as recently shown by Wang et al. ( 139 ) for South Asians.…”

Section: A Future Prospectivementioning

confidence: 99%

Genetic Risk Stratification

Roberts

Chang

Hadley

2021

JACC: Basic to Translational Science

View full text Add to dashboard Cite

show abstract

“…A study of 7,244 South Asian UK Biobank participants derived a PRS of CAD for South Asians from the previous GWAS findings that are primarily European-based. The PRS included 6,630,150 common variants, and demonstrated a successful framework for developing ancestry-specific PRS 63 . In another study, researchers identified significant association between the GRS, which comprised of 29 genome-wide significant blood pressure variants found among European descent, and blood pressure among South Asians 54 .…”

Section: Genetic Basis Of Atherosclerotic Cardiovascular Disease and Heart Failurementioning

confidence: 99%

“…For instance, recent GWAS have been conducted in South Asian diaspora populations, and have contributed to a variety of strategies to understand cardiovascular risk in this population such as polygenic risk scoring (e.g., Wang M et al “Validation of a genome-wide polygenic risk score for coronary artery disease in South Asians.” J Am Coll Cardiol. 2020;76(6):703-14 1 .) This and other recent similar studies would be helpful to include.…”

mentioning

confidence: 99%

Cardiovascular disease risk and pathophysiology in South Asians: can longitudinal multi-omics shed light?

et al. 2021

View full text Add to dashboard Cite

Cardiovascular disease (CVD) is the leading cause of mortality in South Asia, with rapidly increasing prevalence of hypertension, type 2 diabetes (T2DM) and hyperlipidemia over the last two decades. Atherosclerotic CVD (ASCVD) affects South Asians earlier in life and at lower body weights, which is not fully explained by differential burden of conventional risk factors. Heart failure (HF) is a complex clinical syndrome of heterogeneous structural phenotypes including two major clinical subtypes, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). The prevalence of HF in South Asians is also rising with other metabolic diseases, and HFpEF develops at younger age and leaner body mass index in South Asians than in Whites. Recent genome-wide association studies, epigenome-wide association studies and metabolomic studies of ASCVD and HF have identified genes, metabolites and pathways associated with CVD traits. However, these findings were mostly driven by samples of European ancestry, which may not accurately represent the CVD risk at the molecular level, and the unique risk profile of CVD in South Asians. Such bias, while formulating hypothesis-driven research studies, risks missing important causal or predictive factors unique to South Asians. Importantly, a longitudinal design of multi-omic markers can capture the life-course risk and natural history related to CVD, and partially disentangle putative causal relationship between risk factors, multi-omic markers and subclinical and clinical ASCVD and HF. In conclusion, combining high-resolution untargeted metabolomics with epigenomics of rigorous, longitudinal design will provide comprehensive unbiased molecular characterization of subclinical and clinical CVD among South Asians. A thorough understanding of CVD-associated metabolomic profiles, together with advances in epigenomics and genomics, will lead to more accurate estimates of CVD progression and stimulate new strategies for improving cardiovascular health.

show abstract

“…A PRS may be more predictive in one ancestry compared with another, particularly when using variants from a GWAS from an ancestry different to the test population, as causal variants, allele frequencies or effect sizes may significantly vary [11]. A recent study evaluating a CAD PRS derived in South-Asian cohorts identified a significantly increased risk for CAD in individuals in the top 5% of the GRS distribution [31]. However, such studies are rare, often under-powered and require expansion going forward.…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Will Genetic Data Significantly Change Cardiovascular Risk Prediction in Daily Practice?

Young

Ramírez

Duijvenboden

et al. 2020

2020 Computing in Cardiology Conference (CinC)

View full text Add to dashboard Cite

Precision medicine has been heralded as an opportunity to improve risk prediction, driven significantly by an increasing availability of genetic data. Genetic testing for rare mutations linked with Mendelian monogenic syndromes is available in specialised clinics. For complex diseases however, aggregation of common and low frequency variants into a "polygenic risk score" (PRS) is necessary due to their small individual effect sizes. PRSs for coronary artery disease (CAD), hypertension and atrial fibrillation have shown some modest success at a population level. However, scepticism remains whether the genetic effects in CV disease are sufficient to have meaningful clinical impact. This review explores recent efforts to utilise genomic data for risk prediction using CAD as an example.

show abstract

Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

Cited by 83 publications

References 42 publications

Genetic Risk Stratification

Genetic Risk Stratification

Cardiovascular disease risk and pathophysiology in South Asians: can longitudinal multi-omics shed light?

Will Genetic Data Significantly Change Cardiovascular Risk Prediction in Daily Practice?

Contact Info

Product

Resources

About