Portability of 245 polygenic scores when derived from the UK Biobank and applied to 9 ancestry groups from the same cohort

The American Journal of Human Genetics, Journal Year: 2022, Volume and Issue: 109(1), P. 12 - 23

Published: Jan. 1, 2022

Language: Английский

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Leveraging fine-mapping and multipopulation training data to improve cross-population polygenic risk scores

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(4), P. 450 - 458

Published: April 1, 2022

Language: Английский

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Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(11), P. 1640 - 1651

Published: Nov. 1, 2022

Language: Английский

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The complex genetic architecture of Alzheimer's disease: novel insights and future directions

EBioMedicine, Journal Year: 2023, Volume and Issue: 90, P. 104511 - 104511

Published: March 10, 2023

Language: Английский

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Polygenic scoring accuracy varies across the genetic ancestry continuum

Nature, Journal Year: 2023, Volume and Issue: 618(7966), P. 774 - 781

Published: May 17, 2023

Abstract Polygenic scores (PGSs) have limited portability across different groupings of individuals (for example, by genetic ancestries and/or social determinants health), preventing their equitable use 1–3 . PGS has typically been assessed using a single aggregate population-level statistic R 2 ) 4 , ignoring inter-individual variation within the population. Here, large and diverse Los Angeles biobank 5 (ATLAS, n = 36,778) along with UK Biobank 6 (UKBB, 487,409), we show that accuracy decreases individual-to-individual continuum 7 in all considered populations, even traditionally labelled ‘homogeneous’ ancestries. The decreasing trend is well captured continuous measure distance (GD) from training data: Pearson correlation −0.95 between GD averaged 84 traits. When applying models trained on as white British UKBB to European ATLAS, furthest decile 14% lower relative closest decile; notably, Hispanic Latino American similar performance significantly correlated estimates themselves for 82 traits, further emphasizing importance incorporating interpretation. Our results highlight need move away discrete ancestry clusters towards when considering PGSs.

Language: Английский

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Polygenic scores in biomedical research

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(9), P. 524 - 532

Published: March 30, 2022

Language: Английский

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Principles and methods for transferring polygenic risk scores across global populations

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

Published: Aug. 24, 2023

Language: Английский

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A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease

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

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Clinical utility of polygenic risk scores for coronary artery disease

Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 19(5), P. 291 - 301

Published: Nov. 22, 2021

Language: Английский

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Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations

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

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