Addressing overlapping sample challenges in genome-wide association studies: Meta-reductive approach.

Autor: Rajabli F; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States of America.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States of America., Emekci A; Pioneer High School, San Jose, CA, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 01; Vol. 19 (8), pp. e0296207. Date of Electronic Publication: 2024 Aug 01 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0296207
Abstrakt: Polygenic risk scores (PRS) are instrumental in genetics, offering insights into an individual level genetic risk to a range of diseases based on accumulated genetic variations. These scores rely on Genome-Wide Association Studies (GWAS). However, precision in PRS is often challenged by the requirement of extensive sample sizes and the potential for overlapping datasets that can inflate PRS calculations. In this study, we present a novel methodology, Meta-Reductive Approach (MRA), that was derived algebraically to adjust GWAS results, aiming to neutralize the influence of select cohorts. Our approach recalibrates summary statistics using algebraic derivations. Validating our technique with datasets from Alzheimer disease studies, we showed that the summary statistics of the MRA and those derived from individual-level data yielded the exact same values. This innovative method offers a promising avenue for enhancing the accuracy of PRS, especially when derived from meta-analyzed GWAS data.
Competing Interests: The author declares no competing interests.
(Copyright: © 2024 Rajabli, Emekci. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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