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Mixed-model admixture mapping identifies smoking-dependent loci of lung function in African Americans

Abstract : Admixture mapping has led to the discovery of many genes associated with differential disease risk by ancestry, highlighting the importance of ancestry-based approaches to association studies. However, the potential of admixture mapping in deciphering the interplay between genes and environment exposures has been seldom explored. Here we performed a genome-wide screening of local ancestry-smoking interactions for five spirometric lung function phenotypes in 3300 African Americans from the COPDGene study. To account for population structure and outcome heterogeneity across exposure groups, we developed a multi-component linear mixed model for mapping gene-environment interactions and empirically showed its robustness and increased power. When applied to the COPDGene study, our approach identified two 11p15.2-3 and 2q37 loci, exhibiting local ancestry-smoking interactions at genome-wide significant level, which would have been missed by standard single-nucleotide polymorphism analyses. These two loci harbor the PARVA and RAB17 genes previously recognized to be involved in smoking behavior. Overall, our study provides the first evidence for potential synergistic effects between African ancestry and smoking on pulmonary function, and underlines the importance of ethnic diversity in genetic studies.
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Contributor : Amaury Vaysse <>
Submitted on : Friday, June 19, 2020 - 10:07:39 AM
Last modification on : Saturday, June 20, 2020 - 3:30:42 AM

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Andrey Ziyatdinov, Margaret Parker, Amaury Vaysse, Terri Beaty, Peter Kraft, et al.. Mixed-model admixture mapping identifies smoking-dependent loci of lung function in African Americans. European Journal of Human Genetics, Nature Publishing Group, 2020, 28 (5), pp.656-668. ⟨10.1038/s41431-019-0545-8⟩. ⟨pasteur-02874734⟩



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