Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotation
IntroductionPolygenic Scores (PGSs) assess cumulative genetic risk variants that contribute to the association with complex diseases like Alzheimer’s Disease (AD). The PGS Catalog is a valuable repository of PGSs of various complex diseases, but it lacks standardized annotations and harmonization, m...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1507395/full |
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| author | Savannah Mwesigwa Yulin Dai Nitesh Enduru Zhongming Zhao Zhongming Zhao |
| author_facet | Savannah Mwesigwa Yulin Dai Nitesh Enduru Zhongming Zhao Zhongming Zhao |
| author_sort | Savannah Mwesigwa |
| collection | DOAJ |
| description | IntroductionPolygenic Scores (PGSs) assess cumulative genetic risk variants that contribute to the association with complex diseases like Alzheimer’s Disease (AD). The PGS Catalog is a valuable repository of PGSs of various complex diseases, but it lacks standardized annotations and harmonization, making the information difficult to integrate for a specific disease.MethodsIn this study, we curated 44 PGS datasets for AD from the PGS Catalog, categorized them into five methodological groups, and annotated 813,257 variants to nearby genes. We aligned the scores based on the “GWAS significant variants” (GWAS-SV) method with the GWAS Catalog and flagged redundant files and those with a “limited scope” due to insufficient external GWAS support. Using rank aggregation (RA), we prioritized consistently important variants and provided an R package, “PgsRankRnnotatR,” to automate this process.ResultsOf the six RA methods evaluated, “Dowdall” method was the most robust. Our refined dataset, enhanced by multiple RA options, is a valuable resource for AD researchers selecting PGSs or exploring AD-related genetic variants.DiscussionOur approach offers a framework for curating, harmonizing, and prioritizing PGS datasets, improving their usability for AD research. By integrating multiple RA methods and automating the process, we provide a flexible tool that enhances PGS selection and genetic variant exploration. This framework can be extended to other complex diseases or traits, facilitating broader applications in genetic risk assessment. |
| format | Article |
| id | doaj-art-41d4276b1bf74c64b9e8be9d133898d3 |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-41d4276b1bf74c64b9e8be9d133898d32025-02-04T06:32:07ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-02-011610.3389/fgene.2025.15073951507395Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotationSavannah Mwesigwa0Yulin Dai1Nitesh Enduru2Zhongming Zhao3Zhongming Zhao4Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, United StatesCenter for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, United StatesCenter for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, United StatesCenter for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, United StatesFaillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesIntroductionPolygenic Scores (PGSs) assess cumulative genetic risk variants that contribute to the association with complex diseases like Alzheimer’s Disease (AD). The PGS Catalog is a valuable repository of PGSs of various complex diseases, but it lacks standardized annotations and harmonization, making the information difficult to integrate for a specific disease.MethodsIn this study, we curated 44 PGS datasets for AD from the PGS Catalog, categorized them into five methodological groups, and annotated 813,257 variants to nearby genes. We aligned the scores based on the “GWAS significant variants” (GWAS-SV) method with the GWAS Catalog and flagged redundant files and those with a “limited scope” due to insufficient external GWAS support. Using rank aggregation (RA), we prioritized consistently important variants and provided an R package, “PgsRankRnnotatR,” to automate this process.ResultsOf the six RA methods evaluated, “Dowdall” method was the most robust. Our refined dataset, enhanced by multiple RA options, is a valuable resource for AD researchers selecting PGSs or exploring AD-related genetic variants.DiscussionOur approach offers a framework for curating, harmonizing, and prioritizing PGS datasets, improving their usability for AD research. By integrating multiple RA methods and automating the process, we provide a flexible tool that enhances PGS selection and genetic variant exploration. This framework can be extended to other complex diseases or traits, facilitating broader applications in genetic risk assessment.https://www.frontiersin.org/articles/10.3389/fgene.2025.1507395/fullAlzheimer’s diseasegenetic variantPGS catalogpolygenic scoresrank aggregation |
| spellingShingle | Savannah Mwesigwa Yulin Dai Nitesh Enduru Zhongming Zhao Zhongming Zhao Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotation Frontiers in Genetics Alzheimer’s disease genetic variant PGS catalog polygenic scores rank aggregation |
| title | Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotation |
| title_full | Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotation |
| title_fullStr | Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotation |
| title_full_unstemmed | Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotation |
| title_short | Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotation |
| title_sort | enhancing the utility of polygenic scores in alzheimer s disease through systematic curation and annotation |
| topic | Alzheimer’s disease genetic variant PGS catalog polygenic scores rank aggregation |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1507395/full |
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