Rxivist logo

Background: Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains individuals of European ancestry, but the final release (v8) also includes up to 15% of individuals of non-European ancestry. Assessing ancestry-based adjustments in GTEx provides an opportunity to improve portability of this research across populations and to further measure the impact of population structure on GWAS colocalization. Results: Here, we identify a subset of 117 individuals in GTEx (v8) with a high degree of population admixture and estimate genome-wide local ancestry. We perform genome-wide cis-eQTL mapping using admixed samples in six tissues, adjusted by either global or local ancestry. Consistent with previous work, we observe improved power with local ancestry adjustment. At loci where the two adjustments produce different lead variants, we observe only 0.8% of tests with GWAS colocalization posterior probabilities that change by 10% or more. Notably, both adjustments produce similar numbers of significant colocalizations. Finally, we identify a small subset of GTEx v8 eQTL-associated variants highly correlated with local ancestry (R2 > 0.7), providing a resource to enhance functional follow-up. Conclusions: We provide a local ancestry map for admixed individuals in the final GTEx release and describe the impact of ancestry and admixture on gene expression, eQTLs, and GWAS colocalization. While the majority of results are concordant between local and global ancestry-based adjustments, we identify distinct advantages and disadvantages to each approach.

Download data

  • Downloaded 805 times
  • Download rankings, all-time:
    • Site-wide: 23,259 out of 117,931
    • In genetics: 1,208 out of 5,127
  • Year to date:
    • Site-wide: 12,322 out of 117,931
  • Since beginning of last month:
    • Site-wide: 72,695 out of 117,931

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News