Pragmatic Approach to Applying Polygenic Risk Scores to Diverse Populations

Patel, Aniruddh P.; Fahed, Akl C.

doi:10.1002/cpz1.911

Cited by 3 publications

(1 citation statement)

References 83 publications

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“…The rationale is that adjustment for these principal components minimizes genetic association test confounding caused by population stratification. 33 , 34 …”

Section: Methodsmentioning

confidence: 99%

Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial

Zou,

Ruan,

Truong

et al. 2024

JAHA

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Background Coronary artery disease (CAD) is a leading cause of death among the 38.4 million people with HIV globally. The extent to which cardiovascular polygenic risk scores (PRSs) derived in non‐HIV populations generalize to people with HIV is not well understood. Methods and Results PRSs for CAD (GPS Mult ) and lipid traits were calculated in a global cohort of people with HIV treated with antiretroviral therapy with low‐to‐moderate atherosclerotic cardiovascular disease risk enrolled in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV). The PRSs were associated with baseline lipid traits in 4495 genotyped participants, and with subclinical CAD in a subset of 662 who underwent coronary computed tomography angiography. Among participants who underwent coronary computed tomography angiography (mean age, 50.9 [SD, 5.8] years; 16.1% women; 41.8% African, 57.3% European, 1.1% Asian), GPS Mult was associated with plaque presence with odds ratio (OR) per SD in GPS Mult of 1.42 (95% CI, 1.20–1.68; P =3.8×10 −5 ), stenosis >50% (OR, 2.39 [95% CI, 1.48–3.85]; P =3.4×10 −4 ), and noncalcified/vulnerable plaque (OR, 1.45 [95% CI, 1.23–1.72]; P =9.6×10 −6 ). Effects were consistent in subgroups of age, sex, 10‐year atherosclerotic cardiovascular disease risk, ancestry, and CD4 count. Adding GPS Mult to established risk factors increased the C‐statistic for predicting plaque presence from 0.718 to 0.734 ( P =0.02). Furthermore, a PRS for low‐density lipoprotein cholesterol was associated with plaque presence with OR of 1.21 (95% CI, 1.01–1.44; P =0.04), and partially calcified plaque with OR of 1.21 (95% CI, 1.01–1.45; P =0.04) per SD. Conclusions Among people with HIV treated with antiretroviral therapy without documented atherosclerotic cardiovascular disease and at low‐to‐moderate calculated risk in REPRIEVE, an externally developed CAD PRS was predictive of subclinical atherosclerosis. PRS for low‐density lipoprotein cholesterol was also associated with subclinical atherosclerosis, supporting a role for low‐density lipoprotein cholesterol in HIV‐associated CAD. Registration URL: https://www.reprievetrial.org ; Unique identifier: NCT02344290.

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“…The rationale is that adjustment for these principal components minimizes genetic association test confounding caused by population stratification. 33 , 34 …”

Section: Methodsmentioning

confidence: 99%

Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial

Zou,

Ruan,

Truong

et al. 2024

JAHA

Self Cite

View full text Add to dashboard Cite

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Genetic Drivers of Cardiovascular Risk among South Asian Adults

Gami,

Bhattacharya,

Natarajan

et al. 2024

Curr Cardiovasc Risk Rep

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Instability of high polygenic risk classification and mitigation by integrative scoring

Misra,

Truong,

Urbut

et al. 2024

Preprint

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Polygenic risk scores (PRS) continue to improve with novel methods and expanding genome-wide association studies. Healthcare and third-party laboratories are increasingly deploying PRS reports to patients. Although new PRS show improving strengths of association with traits, it is unknown how the classification of high polygenic risk changes across individual PRS for the same trait. Here, we determined classification of high genetic risk from all cataloged PRS for three complex traits. While each PRS for each trait demonstrated generally consistent population-level strengths of associations, classification of individuals in the top 10% of each PRS distribution varied widely. Using the PRSMix framework, which incorporates information across several PRS to improve prediction, we generated sequential add-one-in (AOI) PRSMix_AOI scores based on order of publication. PRSMix_AOIₙ led to improved PRS performance and more consistent high-risk classification compared with the PRSₙ. The PRSMix_AOI approach provides more stable and reliable classification of high-risk as new PRS continue to be generated toward PRS standardization.

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Pragmatic Approach to Applying Polygenic Risk Scores to Diverse Populations

Cited by 3 publications

References 83 publications

Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial

Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial

Genetic Drivers of Cardiovascular Risk among South Asian Adults

Instability of high polygenic risk classification and mitigation by integrative scoring

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