Dataset Information

Assessment of multi-population polygenic risk scores for lipid traits in African Americans.

ABSTRACT: Polygenic risk scores (PRS) based on genome-wide discoveries are promising predictors or classifiers of disease development, severity, and/or progression for common clinical outcomes. A major limitation of most risk scores is the paucity of genome-wide discoveries in diverse populations, prompting an emphasis to generate these needed data for trans-population and population-specific PRS construction. Given diverse genome-wide discoveries are just now being completed, there has been little opportunity for PRS to be evaluated in diverse populations independent from the discovery efforts. To fill this gap, we leverage here summary data from a recent genome-wide discovery study of lipid traits (HDL-C, LDL-C, triglycerides, and total cholesterol) conducted in diverse populations represented by African Americans, Hispanics, Asians, Native Hawaiians, Native Americans, and others by the Population Architecture using Genomics and Epidemiology (PAGE) Study. We constructed lipid trait PRS using PAGE Study published genetic variants and weights in an independent African American adult patient population linked to de-identified electronic health records and genotypes from the Illumina Metabochip (n = 3,254). Using multi-population lipid trait PRS, we assessed levels of association for their respective lipid traits, clinical outcomes (cardiovascular disease and type 2 diabetes), and common clinical labs. While none of the multi-population PRS were strongly associated with the tested trait or outcome, PRS_LDL-Cwas nominally associated with cardiovascular disease. These data demonstrate the complexity in applying PRS to real-world clinical data even when data from multiple populations are available.

SUBMITTER: Drouet DE

PROVIDER: S-EPMC10198155 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Assessment of multi-population polygenic risk scores for lipid traits in African Americans.

Drouet Domenica E DE Liu Shiying S Crawford Dana C DC

PeerJ 20230516

Polygenic risk scores (PRS) based on genome-wide discoveries are promising predictors or classifiers of disease development, severity, and/or progression for common clinical outcomes. A major limitation of most risk scores is the paucity of genome-wide discoveries in diverse populations, prompting an emphasis to generate these needed data for trans-population and population-specific PRS construction. Given diverse genome-wide discoveries are just now being completed, there has been little opport ...[more]

PMID: 37214096

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Project description:Whether the PGS developed using data from European ancestry is predictive of fracture risk for minorities remains unclear. This study demonstrated that PGSs based on common BMD-related genetic variants discovered in the European ancestry cohort are predictive of fracture risk in people of Asian but not African ancestry.PurposeLarge-scale genome-wide association studies (GWAS) on bone mineral density (BMD) have been conducted predominantly in European cohorts. Genetic models based on common variants associated with BMD have been evaluated using almost exclusively European data, which could potentially exacerbate health disparities due to different linkage disequilibrium among different ethnic groups.MethodsUK Biobank (UKB) is a large-scale population-based observational study starting in 2006 that recruited 502,617 individuals aged between 40 and 69 years with genotypic and phenotypic data available. Based on the summary statistics of two GWAS studies of femoral neck BMD and total body BMD, we derived four PGSs and assessed the association between each PGS and prevalent/incident fractures within each ethnic group separately using Multivariate logistic regressions and Cox proportional hazard models. All models were adjusted for age, sex, and the first four principal components.ResultsWe assessed four PGSs derived from European cohorts. Significant associations were observed between PGSs and fracture in European and Asian cohorts but not in the African cohort. Of all four PGSs, [Formula: see text] performed the best. A standard deviation decreases in [Formula: see text] were associated with an increased hazard ratio (HR) of 1.24 (1.22-1.27), 1.28 (0.83-1.99), and 1.34 (1.10-1.64) in European, African, and Asian ancestry, respectively. A low BMD-related PGS is associated with up to 2.35- and 4.31-fold increased fracture risk in European and Asian populations.ConclusionsThese results showed that PGSs based on common BMD-related genetic variants discovered in the European ancestry cohort are predictive of fracture risk in people of Asian but not African ancestry.

Project description:ObjectivePolygenic risk scores (PRS) allow risk stratification using common single-nucleotide polymorphisms (SNPs), and clinical applications are currently explored for several diseases. This study was undertaken to assess the risk of hip and knee osteoarthritis (OA) using PRS.MethodsWe analyzed 12,732 individuals from a population-based cohort from the Rotterdam Study (n = 11,496), a clinical cohort (Cohort Hip and Cohort Knee [CHECK] study; n = 908), and a high-risk cohort of overweight women (Prevention of Knee OA in Overweight Females [PROOF] study; n = 328), for the association of the PRS with prevalence/incidence of radiographic OA, of clinical OA, and of total hip replacement (THR) or total knee replacement (TKR). The hip PRS and knee PRS contained 44 and 24 independent SNPs, respectively, and were derived from a recent genome-wide association study meta-analysis. Standardized PRS (with Z transformation) were used in all analyses.ResultsWe found a stronger association of the PRS for clinically defined OA compared to radiographic OA phenotypes, and we observed the highest PRS risk stratification for TKR/THR. The odds ratio (OR) per SD was 1.3 for incident THR (95% confidence interval [95% CI] 1.1-1.5) and 1.6 (95% CI 1.3-1.9) for incident TKR in the Rotterdam Study. The knee PRS was associated with incident clinical knee OA in the CHECK study (OR 1.3 [95% CI 1.1-1.5]), but not for the PROOF study (OR 1.2 [95% CI 0.8-1.7]). The OR for OA increased gradually across the PRS distribution, up to 2.1 (95% CI 1.4-3.2) for individuals with the 10% highest PRS compared to the middle 50% of the PRS distribution.ConclusionOur findings validated the association of PRS across OA definitions. Since OA is becoming frequent and primary prevention is not commonly applicable, PRS-based risk assessment could play a role in OA prevention. However, the utility of PRS is dependent on the setting. Further studies are needed to test the integration of genetic risk assessment in diverse health care settings.

Dataset Information

Assessment of multi-population polygenic risk scores for lipid traits in African Americans.

Publications

Assessment of multi-population polygenic risk scores for lipid traits in African Americans.

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