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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Aging
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1507395
This article is part of the Research Topic Genetic Underpinnings of Alzheimer's and Parkinson's: Insights and Innovations View all articles

Enhancing the utility of polygenic scores in Alzheimer's disease through systematic curation and annotation

Provisionally accepted
Savannah Mwesigwa Savannah Mwesigwa Yulin Dai Yulin Dai Nitesh Enduru Nitesh Enduru Zhongming Zhao Zhongming Zhao *
  • University of Texas Health Science Center at Houston, Houston, Texas, United States

The final, formatted version of the article will be published soon.

    Polygenic 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. In 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. Of 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. This approach can be applied to other complex diseases or traits.

    Keywords: Alzheimer's disease, Genetic variant, PGS Catalog, polygenic scores, Rank aggregation

    Received: 07 Oct 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Mwesigwa, Dai, Enduru and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhongming Zhao, University of Texas Health Science Center at Houston, Houston, 77030, Texas, United States

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