Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals DOI Creative Commons
Qin Qin Huang,

Neneh Sallah,

Diana Dunca

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 9, 2022

Individuals with South Asian ancestry have a higher risk of heart disease than other groups but been largely excluded from genetic research. Using data 22,000 British Pakistani and Bangladeshi individuals linked electronic health records the Genes & Health cohort, we conducted genome-wide association studies coronary artery its key factors. power-adjusted transferability ratios, found evidence for majority cardiometabolic loci powered to replicate. The performance polygenic scores was high lipids blood pressure, lower BMI disease. Adding score clinical factors showed significant improvement in reclassification. In Mendelian randomisation using transferable as instruments, our findings were consistent results European-ancestry individuals. Taken together, trait-specific trait between populations is an important consideration implications prediction causal inference.

Language: Английский

Improving polygenic prediction in ancestrally diverse populations DOI
Yunfeng Ruan, Kuang Lin, Yen‐Chen Anne Feng

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(5), P. 573 - 580

Published: May 1, 2022

Language: Английский

Citations

428
Principles and methods for transferring polygenic risk scores across global populations DOI
Linda Kachuri, Nilanjan Chatterjee, Jibril Hirbo

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 8 - 25

Published: Aug. 24, 2023

Language: Английский

Citations

132
A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease DOI Creative Commons
Aniruddh P. Patel, Minxian Wang, Yunfeng Ruan

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(7), P. 1793 - 1803

Published: July 1, 2023

Abstract Identification of individuals at highest risk coronary artery disease (CAD)—ideally before onset—remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable stratification, reflecting the substantial inherited component CAD risk. Here we develop a new and significantly improved score for CAD, termed GPS Mult , that incorporates association data across five ancestries (>269,000 cases >1,178,000 controls) ten factors. strongly associated with prevalent (odds ratio per standard deviation 2.14, 95% confidence interval 2.10–2.19, P < 0.001) in UK Biobank participants European ancestry, identifying 20.0% population 3-fold increased conversely 13.9% decreased as compared those middle quintile. was also incident events (hazard 1.73, 1.70–1.76, 0.001), 3% healthy future equivalent existing improving discrimination reclassification. Across multiethnic, external validation datasets inclusive 33,096, 124,467, 16,433 16,874 African, European, Hispanic South Asian respectively, demonstrated strength associations all outperformed available previously published scores. These contribute field provide generalizable framework how large-scale integration genetic related traits from diverse populations can meaningfully improve prediction.

Language: Английский

Citations

118
Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations DOI Creative Commons
Tian Ge, Marguerite R. Irvin, Amit Patki

et al.

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: June 28, 2022

Abstract Background Type 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic scores (PRS) have shown promise to complement established clinical intervention paradigms, improve early diagnosis prevention T2D. However, date, T2D PRS been most widely developed validated in individuals European descent. Comprehensive assessment non-European populations critical for equitable deployment practice benefits global populations. Methods We integrated GWAS European, African, East Asian construct trans-ancestry using newly Bayesian modeling method, assessed the prediction accuracy multi-ethnic Electronic Medical Records Genomics (eMERGE) study (11,945 cases; 57,694 controls), four Black cohorts (5137 9657 Taiwan Biobank (4570 84,996 controls). additionally evaluated post hoc ancestry adjustment method can express on same scale across ancestrally diverse facilitate implementation prospective cohorts. Results The was significantly associated with status ancestral groups examined. top 2% distribution identify an approximately 2.5–4.5-fold increase risk, which corresponds increased first-degree relatives. eliminated major distributional differences ancestries without compromising its predictive performance. Conclusions By integrating from multiple populations, we PRS, demonstrated potential as meaningful index among patients settings. Our efforts represent first step towards into routine healthcare.

Language: Английский

Citations

110
Challenges and Opportunities for Developing More Generalizable Polygenic Risk Scores DOI
Ying Wang, Kristin Tsuo, Masahiro Kanai

et al.

Annual Review of Biomedical Data Science, Journal Year: 2022, Volume and Issue: 5(1), P. 293 - 320

Published: May 16, 2022

Polygenic risk scores (PRS) estimate an individual's genetic likelihood of complex traits and diseases by aggregating information across multiple variants identified from genome-wide association studies. PRS can predict a broad spectrum have therefore been widely used in research settings. Some work has investigated their potential applications as biomarkers preventative medicine, but significant is still needed to definitively establish communicate absolute patients for modifiable factors demographic groups. However, the biggest limitation currently that they show poor generalizability diverse ancestries cohorts. Major efforts are underway through methodological development data generation initiatives improve generalizability. This review aims comprehensively discuss current progress on PRS, affect generalizability, promising areas improving accuracy, portability, implementation.

Language: Английский

Citations

100
Recommendations on the use and reporting of race, ethnicity, and ancestry in genetic research: Experiences from the NHLBI TOPMed program DOI Creative Commons
Alyna Khan, Stephanie M. Gogarten, Caitlin McHugh

et al.

Cell Genomics, Journal Year: 2022, Volume and Issue: 2(8), P. 100155 - 100155

Published: July 26, 2022

How race, ethnicity, and ancestry are used in genomic research has wide-ranging implications for how is translated into clinical care incorporated public understanding. Correlation between race genetic contributes to unresolved complexity the scientific community, as illustrated by heterogeneous definitions applications of these variables. Here, we offer commentary recommendations on use across arc research, including data harmonization, analysis, reporting. While informed our experiences researchers affiliated with NHLBI Trans-Omics Precision Medicine (TOPMed) program, applicable basic translational diverse populations genome-wide data. Moving forward, considerable collaborative effort will be required ensure that described appropriately generate knowledge yields broad equitable benefit.

Language: Английский

Citations

79
Leveraging base-pair mammalian constraint to understand genetic variation and human disease DOI
Patrick F. Sullivan, Jennifer R. S. Meadows, Steven Gazal

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6643)

Published: April 27, 2023

Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability discern which positions functionally important. Evolutionary constraint is a powerful predictor function, agnostic cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% the genome as significantly constrained and likely functional. We compared annotation, association studies, copy-number variation, clinical genetics findings, cancer data. Constrained enriched for variants that explain common heritability more than other functional annotations. Our results improve variant annotation also highlight regulatory landscape still needs be further explored linked disease.

Language: Английский

Citations

69
Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts DOI Creative Commons
Ying Wang, Shinichi Namba, Esteban A. Lopera-Maya

et al.

Cell Genomics, Journal Year: 2023, Volume and Issue: 3(1), P. 100241 - 100241

Published: Jan. 1, 2023

Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies thoroughly investigated their best practices global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance 9 biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning thresholding (P + T) PRS-continuous shrinkage (CS). For both methods, a European-based linkage disequilibrium (LD) reference panel resulted comparable or higher prediction accuracy compared with several other non-European-based panels. PRS-CS overall outperformed the classic P T method, especially endpoints SNP-based heritability. Notably, is heterogeneous endpoints, biobanks, ancestries, asthma, which has known variation prevalence populations. Overall, provide lessons construction, evaluation, interpretation GBMI resources highlight importance of biobank-scale genomics era.

Language: Английский

Citations

68
A new method for multiancestry polygenic prediction improves performance across diverse populations DOI
Haoyu Zhang, Jianan Zhan, Jin Jin

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(10), P. 1757 - 1768

Published: Sept. 25, 2023

Language: Английский

Citations

47
Genome-wide association studies of cardiovascular disease DOI
Roddy Walsh, Sean J. Jurgens, Jeanette Erdmann

et al.

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(3), P. 2039 - 2055

Published: Jan. 12, 2023

Genome-wide association studies (GWAS) aim to identify common genetic variants that are associated with traits and diseases. Since 2005, more than 5,000 GWAS have been published for almost as many traits. These offered insights into the loci genes underlying phenotypic traits, highlighted correlations across diseases, beginning demonstrate clinical utility by identifying individuals at increased risk widely utilized cardiovascular diseases facilitated multicenter registry large biobank data sets. In this review, we describe how informed architecture of they provided disease pathophysiology, using archetypal conditions both rare We also sets can complement disease-specific studies, particularly rarer findings from potential impact on care. Finally, discuss outstanding challenges facing research in field be addressed.

Language: Английский

Citations

44