Mar 29, 2020

Population structure and pharmacogenomic risk stratification in the United States

BioRxiv : the Preprint Server for Biology
S. D. NagarI. King Jordan

Abstract

Pharmacogenomic (PGx) variants mediate how individuals respond to medication, and response differences among racial/ethnic groups have been attributed to patterns of PGx diversity. We hypothesized that genetic ancestry (GA) would provide higher resolution for stratifying PGx risk, since it serves as a more reliable surrogate for genetic diversity than self-identified race/ethnicity (SIRE), which includes a substantial social component. We analyzed a cohort of 8,628 individuals from the United States (US), for whom we had both SIRE information and whole genome genotypes, with a focus on the three largest SIRE groups in the US: White, Black, and Hispanic. Whole genome genotypes were used to characterize individuals' continental ancestry fractions - European, African, and Native American - and individuals were grouped according to their GA profiles. SIRE and GA groups were found to be highly concordant. Continental ancestry predicts individuals' SIRE with >96% accuracy, and accordingly GA provides only a marginal increase in resolution for PGx risk stratification. PGx variants are highly diverged compared to the genomic background; 82 variants show significant frequency differences among SIRE groups, and genome-wide patterns of PG...Continue Reading

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Mentioned in this Paper

Study
Pongidae
Research
Genome
PRDM9 gene
Divergence
Western Blotting
Dysequilibrium Syndrome
Genome Assembly Sequence
Recombination, Genetic

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