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While the majority of the results are concordant between local and global ancestry-based adjustments, we identify distinct advantages and disadvantages to each approach. We provide a local ancestry map for admixed individuals in the GTEx v8 release and describe the impact of ancestry and admixture on gene expression, eQTLs, and GWAS colocalization. Finally, we identify a small subset of eQTL-associated variants highly correlated with local ancestry, providing a resource to enhance functional follow-up. Notably, both adjustments produce similar numbers of significant colocalizations within each of two different colocalization methods, COLOC and FINEMAP.
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At loci where the two adjustments produce different lead variants, we observe 31 loci (0.02%) where a significant colocalization is called only with one eQTL ancestry adjustment method. Consistent with previous work, we observe improved power with local ancestry adjustment. We perform genome-wide cis-eQTL mapping using admixed samples in seven tissues, adjusted by either global or local ancestry. Here, we identify a subset of 117 individuals in GTEx (v8) with a high degree of population admixture and estimate genome-wide local ancestry. Assessing ancestry-based adjustments in GTEx improves portability of this research across populations and further characterizes the impact of population structure on GWAS colocalization. The Genotype-Tissue Expression (GTEx) project largely contains individuals of European ancestry, but the v8 release also includes up to 15% of individuals of non-European ancestry.
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Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings.