Language

English

Publication Date

5-3-2026

Journal

Bioinformatics

DOI

10.1093/bioinformatics/btag124

PMID

41838407

PMCID

PMC13197121

PubMedCentral® Posted Date

3-16-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Motivation: The routine exclusion of admixed individuals from traditional genome-wide association studies (GWAS) due to concerns about spurious associations has limited multi-ancestry genetic discovery. Tractor addresses this issue by incorporating local ancestry into association testing, enabling the identification of ancestry-enriched signals and generating ancestry-specific summary statistics. However, adoption has been constrained by the complexity of prerequisite steps, including phasing and local ancestry inference, which require substantial bioinformatics expertise and introduce key analytical decision points.

Results: We developed a scalable, automated Nextflow workflow that integrates phasing, local ancestry inference, and Tractor association testing into a reproducible end-to-end pipeline. To demonstrate its utility, we applied the workflow to 32 blood biomarkers in 6245 two-way African-European admixed individuals from the UK Biobank. This pipeline performed efficiently at scale, replicating known associations and uncovering key ancestry-specific loci. These associations were largely driven by variants present on African ancestral tracts but absent from European tracts, underscoring the value of local ancestry-aware methods in uncovering previously masked genetic signals.

Availability and implementation: The workflow is modular, customizable, and compatible with commonly used phasing and local ancestry tools, minimizing manual intervention while preserving analytical flexibility. By lowering technical barriers to implementation, this framework facilitates broader adoption of local ancestry-aware GWAS, paving the way for expanded genetic discovery.

Keywords

Genome-Wide Association Study, Humans, Software, Workflow, Polymorphism, Single Nucleotide, Computational Biology, UK Biobank, African People

Published Open-Access

yes

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