Generalizing polygenic risk scores from Europeans to Hispanics/Latinos

Kelsey E. Grinde, Qibin Qi, Timothy A. Thornton, Simin Liu, Aladdin H. Shadyab, Kei Hang K. Chan, Alexander P. Reiner, Tamar Sofer

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Polygenic risk scores (PRSs) are weighted sums of risk allele counts of single-nucleotide polymorphisms (SNPs) associated with a disease or trait. PRSs are typically constructed based on published results from Genome-Wide Association Studies (GWASs), and the majority of which has been performed in large populations of European ancestry (EA) individuals. Although many genotype-trait associations have generalized across populations, the optimal choice of SNPs and weights for PRSs may differ between populations due to different linkage disequilibrium (LD) and allele frequency patterns. We compare various approaches for PRS construction, using GWAS results from both large EA studies and a smaller study in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL, n = 12, 803). We consider multiple approaches for selecting SNPs and for computing SNP weights. We study the performance of the resulting PRSs in an independent study of Hispanics/Latinos from the Women’s Health Initiative (WHI, n = 3, 582). We support our investigation with simulation studies of potential genetic architectures in a single locus. We observed that selecting variants based on EA GWASs generally performs well, except for blood pressure trait. However, the use of EA GWASs for weight estimation was suboptimal. Using non-EA GWAS results to estimate weights improved results.

Original languageEnglish (US)
JournalGenetic Epidemiology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Hispanic Americans
Genome-Wide Association Study
Single Nucleotide Polymorphism
Weights and Measures
Population
Linkage Disequilibrium
Women's Health
Gene Frequency
Alleles
Genotype
Blood Pressure
Health

Keywords

  • admixed populations
  • genetic diversity
  • linkage disequilibrium

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

Cite this

Grinde, K. E., Qi, Q., Thornton, T. A., Liu, S., Shadyab, A. H., Chan, K. H. K., ... Sofer, T. (Accepted/In press). Generalizing polygenic risk scores from Europeans to Hispanics/Latinos. Genetic Epidemiology. https://doi.org/10.1002/gepi.22166

Generalizing polygenic risk scores from Europeans to Hispanics/Latinos. / Grinde, Kelsey E.; Qi, Qibin; Thornton, Timothy A.; Liu, Simin; Shadyab, Aladdin H.; Chan, Kei Hang K.; Reiner, Alexander P.; Sofer, Tamar.

In: Genetic Epidemiology, 01.01.2018.

Research output: Contribution to journalArticle

Grinde, KE, Qi, Q, Thornton, TA, Liu, S, Shadyab, AH, Chan, KHK, Reiner, AP & Sofer, T 2018, 'Generalizing polygenic risk scores from Europeans to Hispanics/Latinos', Genetic Epidemiology. https://doi.org/10.1002/gepi.22166
Grinde, Kelsey E. ; Qi, Qibin ; Thornton, Timothy A. ; Liu, Simin ; Shadyab, Aladdin H. ; Chan, Kei Hang K. ; Reiner, Alexander P. ; Sofer, Tamar. / Generalizing polygenic risk scores from Europeans to Hispanics/Latinos. In: Genetic Epidemiology. 2018.
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