Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-differential effects via GAUDI

Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we de...

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Vydáno v:Nature communications Ročník 15; číslo 1; s. 1016 - 14
Hlavní autoři: Sun, Quan, Rowland, Bryce T., Chen, Jiawen, Mikhaylova, Anna V., Avery, Christy, Peters, Ulrike, Lundin, Jessica, Matise, Tara, Buyske, Steve, Tao, Ran, Mathias, Rasika A., Reiner, Alexander P., Auer, Paul L., Cox, Nancy J., Kooperberg, Charles, Thornton, Timothy A., Raffield, Laura M., Li, Yun
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 03.02.2024
Nature Publishing Group
Nature Portfolio
Témata:
45
45/43
631/114/2415
631/208/480
631/208/721
C-reactive protein
Genomes
Health promotion
Humanities and Social Sciences
Leukocytes
multidisciplinary
Polygenic inheritance
Risk
Science
Science (multidisciplinary)
Segments
ISSN:2041-1723, 2041-1723
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Shrnutí:Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals. GAUDI explicitly models ancestry-differential effects while borrowing information across segments with shared ancestry in admixed genomes. We demonstrate marked advantages of GAUDI over other methods through comprehensive simulation and real data analyses for traits with associated variants exhibiting ancestral-differential effects. Leveraging data from the Women’s Health Initiative study, we show that GAUDI improves PRS prediction of white blood cell count and C-reactive protein in African Americans by > 64% compared to alternative methods, and even outperforms PRS-CSx with large European GWAS for some scenarios. We believe GAUDI will be a valuable tool to mitigate disparities in PRS performance in admixed individuals. Most polygenic risk score (PRS) methods focus only on individuals with distinct primary continental ancestry, without accommodating recently-admixed individuals. Here, the authors develop a novel penalized regression-based PRS method specifically designed for admixed individuals.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-45135-z