Tractor uses local ancestry to enable the inclusion of admixed individuals in GWAS and to boost power

Admixed populations are routinely excluded from genomic studies due to concerns over population structure. Here, we present a statistical framework and software package, Tractor, to facilitate the inclusion of admixed individuals in association studies by leveraging local ancestry. We test Tractor w...

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Veröffentlicht in:Nature genetics 2021-02, Vol.53 (2), p.195-204
Hauptverfasser: Atkinson, Elizabeth G., Maihofer, Adam X., Kanai, Masahiro, Martin, Alicia R., Karczewski, Konrad J., Santoro, Marcos L., Ulirsch, Jacob C., Kamatani, Yoichiro, Okada, Yukinori, Finucane, Hilary K., Koenen, Karestan C., Nievergelt, Caroline M., Daly, Mark J., Neale, Benjamin M.
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Sprache:eng
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Zusammenfassung:Admixed populations are routinely excluded from genomic studies due to concerns over population structure. Here, we present a statistical framework and software package, Tractor, to facilitate the inclusion of admixed individuals in association studies by leveraging local ancestry. We test Tractor with simulated and empirical two-way admixed African–European cohorts. Tractor generates accurate ancestry-specific effect-size estimates and P  values, can boost genome-wide association study (GWAS) power and improves the resolution of association signals. Using a local ancestry-aware regression model, we replicate known hits for blood lipids, discover novel hits missed by standard GWAS and localize signals closer to putative causal variants. Tractor is a statistical framework that facilitates the inclusion of admixed individuals in association studies by leveraging local ancestry. Tractor generates accurate ancestry-specific effect-size estimates and improves the resolution of association signals.
ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/s41588-020-00766-y