Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments
Abstract Clinical implementation of new prediction models requires evaluation of their utility in a broad range of intended use populations. Here we develop and validate ancestry-specific Polygenic Risk Scores (PRSs) for Coronary Artery Disease (CAD) using 29,389 individuals from diverse cohorts and...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42897-w |
| _version_ | 1827770436062019584 |
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| author | George B. Busby Scott Kulm Alessandro Bolli Jen Kintzle Paolo Di Domenico Giordano Bottà |
| author_facet | George B. Busby Scott Kulm Alessandro Bolli Jen Kintzle Paolo Di Domenico Giordano Bottà |
| author_sort | George B. Busby |
| collection | DOAJ |
| description | Abstract Clinical implementation of new prediction models requires evaluation of their utility in a broad range of intended use populations. Here we develop and validate ancestry-specific Polygenic Risk Scores (PRSs) for Coronary Artery Disease (CAD) using 29,389 individuals from diverse cohorts and genetic ancestry groups. The CAD PRSs outperform published scores with an average Odds Ratio per Standard Deviation of 1.57 (SD = 0.14) and identify between 12% and 24% of individuals with high genetic risk. Using this risk factor to reclassify borderline or intermediate 10 year Atherosclerotic Cardiovascular Disease (ASCVD) risk improves assessments for both CAD (Net Reclassification Improvement (NRI) = 13.14% (95% CI 9.23–17.06%)) and ASCVD (NRI = 10.70 (95% CI 7.35-14.05)) in an independent cohort of 9,691 individuals. Our analyses demonstrate that using PRSs as Risk Enhancers improves ASCVD risk assessments outlining an approach for guiding ASCVD prevention with genetic information. |
| first_indexed | 2024-03-11T12:39:31Z |
| format | Article |
| id | doaj.art-44e7791f217540b3aa1a466ee00c865a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T12:39:31Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-44e7791f217540b3aa1a466ee00c865a2023-11-05T12:22:50ZengNature PortfolioNature Communications2041-17232023-11-0114111110.1038/s41467-023-42897-wAncestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessmentsGeorge B. Busby0Scott Kulm1Alessandro Bolli2Jen Kintzle3Paolo Di Domenico4Giordano Bottà5Allelica IncAllelica IncAllelica IncAllelica IncAllelica IncAllelica IncAbstract Clinical implementation of new prediction models requires evaluation of their utility in a broad range of intended use populations. Here we develop and validate ancestry-specific Polygenic Risk Scores (PRSs) for Coronary Artery Disease (CAD) using 29,389 individuals from diverse cohorts and genetic ancestry groups. The CAD PRSs outperform published scores with an average Odds Ratio per Standard Deviation of 1.57 (SD = 0.14) and identify between 12% and 24% of individuals with high genetic risk. Using this risk factor to reclassify borderline or intermediate 10 year Atherosclerotic Cardiovascular Disease (ASCVD) risk improves assessments for both CAD (Net Reclassification Improvement (NRI) = 13.14% (95% CI 9.23–17.06%)) and ASCVD (NRI = 10.70 (95% CI 7.35-14.05)) in an independent cohort of 9,691 individuals. Our analyses demonstrate that using PRSs as Risk Enhancers improves ASCVD risk assessments outlining an approach for guiding ASCVD prevention with genetic information.https://doi.org/10.1038/s41467-023-42897-w |
| spellingShingle | George B. Busby Scott Kulm Alessandro Bolli Jen Kintzle Paolo Di Domenico Giordano Bottà Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments Nature Communications |
| title | Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments |
| title_full | Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments |
| title_fullStr | Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments |
| title_full_unstemmed | Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments |
| title_short | Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments |
| title_sort | ancestry specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments |
| url | https://doi.org/10.1038/s41467-023-42897-w |
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