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Accounting for genetic effect heterogeneity in fine-mapping and improving power to detect gene-environment interactions with SharePro

Author

Listed:
  • Wenmin Zhang

    (McGill University
    Montreal Heart Institute)

  • Robert Sladek

    (McGill University
    McGill University
    McGill University)

  • Yue Li

    (McGill University
    McGill University)

  • Hamed Najafabadi

    (McGill University
    McGill University
    McGill University)

  • Josée Dupuis

    (McGill University
    McGill University)

Abstract

Classical gene-by-environment interaction (GxE) analysis can be used to characterize genetic effect heterogeneity but has a high multiple testing burden in the context of genome-wide association studies (GWAS). We adapt a colocalization method, SharePro, to account for effect heterogeneity in fine-mapping and identify candidates for GxE analysis with reduced multiple testing burden. SharePro demonstrates improved power for both fine-mapping and GxE analysis compared to existing methods as well as well-controlled false type I error in simulations. Using smoking status stratified GWAS summary statistics, we identify genetic effects on lung function modulated by smoking status that are not identified by existing methods. Additionally, using sex stratified GWAS summary statistics, we characterize sex differentiated genetic effects on fat distribution. In summary, we have developed an analytical framework to account for effect heterogeneity in fine-mapping and subsequently improve power for GxE analysis. The SharePro software for GxE analysis is openly available at https://github.com/zhwm/SharePro_gxe .

Suggested Citation

  • Wenmin Zhang & Robert Sladek & Yue Li & Hamed Najafabadi & Josée Dupuis, 2024. "Accounting for genetic effect heterogeneity in fine-mapping and improving power to detect gene-environment interactions with SharePro," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53818-w
    DOI: 10.1038/s41467-024-53818-w
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    References listed on IDEAS

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