Johanna L Smith, Catherine Tcheandjieu, Ozan Dikilitas, Kruthika Iyer, Kazuo Miyazawa, Austin Hilliard, Julie Lynch, Jerome I Rotter, Yii-Der Ida Chen, Wayne Huey-Herng Sheu, Kyong-Mi Chang, Stavroula Kanoni, Philip S Tsao, Kaoru Ito, Matthew Kosel, Shoa L Clarke, Daniel J Schaid, Themistocles L Assimes, Iftikhar J Kullo
{"title":"基于祖先多样性全基因组关联研究和特定人群优化的冠心病多祖先多基因风险评分。","authors":"Johanna L Smith, Catherine Tcheandjieu, Ozan Dikilitas, Kruthika Iyer, Kazuo Miyazawa, Austin Hilliard, Julie Lynch, Jerome I Rotter, Yii-Der Ida Chen, Wayne Huey-Herng Sheu, Kyong-Mi Chang, Stavroula Kanoni, Philip S Tsao, Kaoru Ito, Matthew Kosel, Shoa L Clarke, Daniel J Schaid, Themistocles L Assimes, Iftikhar J Kullo","doi":"10.1161/CIRCGEN.123.004272","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRS<sub>CHD</sub>) for 5 genetic ancestry groups.</p><p><strong>Methods: </strong>We derived ancestry-specific and multi-ancestry PRS<sub>CHD</sub> based on pruning and thresholding (PRS<sub>PT</sub>) and ancestry-based continuous shrinkage priors (PRS<sub>CSx</sub>) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.1 million participants from 5 major genetic ancestry groups. Following training and optimization in the Million Veteran Program, we evaluated the best-performing PRS<sub>CHD</sub> in 176,988 individuals across 9 diverse cohorts.</p><p><strong>Results: </strong>Multi-ancestry PRS<sub>PT</sub> and PRS<sub>CSx</sub> outperformed ancestry-specific PRS<sub>PT</sub> and PRS<sub>CSx</sub> across a range of tuning values. Two best-performing multi-ancestry PRS<sub>CHD</sub> (ie, PRS<sub>PTmult</sub> and PRS<sub>CSxmult</sub>) and 1 ancestry-specific (PRS<sub>CSxEUR</sub>) were taken forward for validation. PRS<sub>PTmult</sub> demonstrated the strongest association with CHD in individuals of South Asian ancestry and European ancestry (odds ratio per 1 SD [95% CI, 2.75 [2.41-3.14], 1.65 [1.59-1.72]), followed by East Asian ancestry (1.56 [1.50-1.61]), Hispanic/Latino ancestry (1.38 [1.24-1.54]), and African ancestry (1.16 [1.11-1.21]). PRS<sub>CSxmult</sub> showed the strongest associations in South Asian ancestry (2.67 [2.38-3.00]) and European ancestry (1.65 [1.59-1.71]), lower in East Asian ancestry (1.59 [1.54-1.64]), Hispanic/Latino ancestry (1.51 [1.35-1.69]), and the lowest in African ancestry (1.20 [1.15-1.26]).</p><p><strong>Conclusions: </strong>The use of summary statistics from a large multi-ancestry genome-wide meta-analysis improved the performance of PRS<sub>CHD</sub> in most ancestry groups compared with single-ancestry methods. Despite the use of one of the largest and most diverse sets of training and validation cohorts to date, improvement of predictive performance was limited in African ancestry. This highlights the need for larger genome-wide association study datasets of underrepresented populations to enhance the performance of PRS<sub>CHD</sub>.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372723/pdf/","citationCount":"0","resultStr":"{\"title\":\"Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization.\",\"authors\":\"Johanna L Smith, Catherine Tcheandjieu, Ozan Dikilitas, Kruthika Iyer, Kazuo Miyazawa, Austin Hilliard, Julie Lynch, Jerome I Rotter, Yii-Der Ida Chen, Wayne Huey-Herng Sheu, Kyong-Mi Chang, Stavroula Kanoni, Philip S Tsao, Kaoru Ito, Matthew Kosel, Shoa L Clarke, Daniel J Schaid, Themistocles L Assimes, Iftikhar J Kullo\",\"doi\":\"10.1161/CIRCGEN.123.004272\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRS<sub>CHD</sub>) for 5 genetic ancestry groups.</p><p><strong>Methods: </strong>We derived ancestry-specific and multi-ancestry PRS<sub>CHD</sub> based on pruning and thresholding (PRS<sub>PT</sub>) and ancestry-based continuous shrinkage priors (PRS<sub>CSx</sub>) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.1 million participants from 5 major genetic ancestry groups. Following training and optimization in the Million Veteran Program, we evaluated the best-performing PRS<sub>CHD</sub> in 176,988 individuals across 9 diverse cohorts.</p><p><strong>Results: </strong>Multi-ancestry PRS<sub>PT</sub> and PRS<sub>CSx</sub> outperformed ancestry-specific PRS<sub>PT</sub> and PRS<sub>CSx</sub> across a range of tuning values. Two best-performing multi-ancestry PRS<sub>CHD</sub> (ie, PRS<sub>PTmult</sub> and PRS<sub>CSxmult</sub>) and 1 ancestry-specific (PRS<sub>CSxEUR</sub>) were taken forward for validation. PRS<sub>PTmult</sub> demonstrated the strongest association with CHD in individuals of South Asian ancestry and European ancestry (odds ratio per 1 SD [95% CI, 2.75 [2.41-3.14], 1.65 [1.59-1.72]), followed by East Asian ancestry (1.56 [1.50-1.61]), Hispanic/Latino ancestry (1.38 [1.24-1.54]), and African ancestry (1.16 [1.11-1.21]). PRS<sub>CSxmult</sub> showed the strongest associations in South Asian ancestry (2.67 [2.38-3.00]) and European ancestry (1.65 [1.59-1.71]), lower in East Asian ancestry (1.59 [1.54-1.64]), Hispanic/Latino ancestry (1.51 [1.35-1.69]), and the lowest in African ancestry (1.20 [1.15-1.26]).</p><p><strong>Conclusions: </strong>The use of summary statistics from a large multi-ancestry genome-wide meta-analysis improved the performance of PRS<sub>CHD</sub> in most ancestry groups compared with single-ancestry methods. Despite the use of one of the largest and most diverse sets of training and validation cohorts to date, improvement of predictive performance was limited in African ancestry. This highlights the need for larger genome-wide association study datasets of underrepresented populations to enhance the performance of PRS<sub>CHD</sub>.</p>\",\"PeriodicalId\":10326,\"journal\":{\"name\":\"Circulation: Genomic and Precision Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372723/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation: Genomic and Precision Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCGEN.123.004272\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Genomic and Precision Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCGEN.123.004272","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/21 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization.
Background: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRSCHD) for 5 genetic ancestry groups.
Methods: We derived ancestry-specific and multi-ancestry PRSCHD based on pruning and thresholding (PRSPT) and ancestry-based continuous shrinkage priors (PRSCSx) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.1 million participants from 5 major genetic ancestry groups. Following training and optimization in the Million Veteran Program, we evaluated the best-performing PRSCHD in 176,988 individuals across 9 diverse cohorts.
Results: Multi-ancestry PRSPT and PRSCSx outperformed ancestry-specific PRSPT and PRSCSx across a range of tuning values. Two best-performing multi-ancestry PRSCHD (ie, PRSPTmult and PRSCSxmult) and 1 ancestry-specific (PRSCSxEUR) were taken forward for validation. PRSPTmult demonstrated the strongest association with CHD in individuals of South Asian ancestry and European ancestry (odds ratio per 1 SD [95% CI, 2.75 [2.41-3.14], 1.65 [1.59-1.72]), followed by East Asian ancestry (1.56 [1.50-1.61]), Hispanic/Latino ancestry (1.38 [1.24-1.54]), and African ancestry (1.16 [1.11-1.21]). PRSCSxmult showed the strongest associations in South Asian ancestry (2.67 [2.38-3.00]) and European ancestry (1.65 [1.59-1.71]), lower in East Asian ancestry (1.59 [1.54-1.64]), Hispanic/Latino ancestry (1.51 [1.35-1.69]), and the lowest in African ancestry (1.20 [1.15-1.26]).
Conclusions: The use of summary statistics from a large multi-ancestry genome-wide meta-analysis improved the performance of PRSCHD in most ancestry groups compared with single-ancestry methods. Despite the use of one of the largest and most diverse sets of training and validation cohorts to date, improvement of predictive performance was limited in African ancestry. This highlights the need for larger genome-wide association study datasets of underrepresented populations to enhance the performance of PRSCHD.
期刊介绍：
Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations.
Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
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