Title | Generalizing polygenic risk scores from Europeans to Hispanics/Latinos. |
Publication Type | Publication |
Year | 2019 |
Authors | Grinde KE, Qi Q, Thornton TA, Liu S, Shadyab AH, Chan KHang K, Reiner AP, Sofer T |
Journal | Genet Epidemiol |
Volume | 43 |
Issue | 1 |
Pagination | 50-62 |
Date Published | 2019 Feb |
ISSN | 1098-2272 |
Keywords | Computer Simulation, genome-wide association study, Hispanic or Latino, Humans, Linkage Disequilibrium, Models, Genetic, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, White People |
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, ). 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, ). 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. |
DOI | 10.1002/gepi.22166 |
Alternate Journal | Genet Epidemiol |
PubMed ID | 30368908 |
PubMed Central ID | PMC6330129 |
Grant List | N01HC65236 / HL / NHLBI NIH HHS / United States N01HC65235 / HL / NHLBI NIH HHS / United States N01HC65234 / HL / NHLBI NIH HHS / United States R35 HL135818 / HL / NHLBI NIH HHS / United States N01HC65233 / HL / NHLBI NIH HHS / United States HL120393-03S1 / HL / NHLBI NIH HHS / United States HHSN268201100004C / HL / NHLBI NIH HHS / United States HHSN268201300004I/N01-HC-65234 / NH / NIH HHS / United States R01HG005827 / HG / NHGRI NIH HHS / United States HG006292 / HG / NHGRI NIH HHS / United States / MD / NIMHD NIH HHS / United States R01 HG006292 / HG / NHGRI NIH HHS / United States HHSC271201100004C / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States / DC / NIDCD NIH HHS / United States AM03 and MOD03 / HL / NHLBI NIH HHS / United States / DE / NIDCR NIH HHS / United States HHSN268201300005I/N01-HC-65237 / NH / NIH HHS / United States R01 HL129132 / HL / NHLBI NIH HHS / United States HHSN268201100003C / HL / NHLBI NIH HHS / United States N01HC65237 / HL / NHLBI NIH HHS / United States HHSN268201300003I/N01-HC-65236 / NH / NIH HHS / United States HHSN268201300001I/N01-HC-65233 / HL / NHLBI NIH HHS / United States 1R35HL135818 HHSN268201100046C / HL / NHLBI NIH HHS / United States HHSN268201100001C / HL / NHLBI NIH HHS / United States / NS / NINDS NIH HHS / United States T32 GM081062 / GM / NIGMS NIH HHS / United States R01 HG005827 / HG / NHGRI NIH HHS / United States HL129132 / HG / NHGRI NIH HHS / United States HHSN268201100002C / HL / NHLBI NIH HHS / United States / DK / NIDDK NIH HHS / United States HHSN268201300002I/N01-HC-65235 / NH / NIH HHS / United States |
Generalizing polygenic risk scores from Europeans to Hispanics/Latinos.
MS#:
0504
ECI:
Yes
Manuscript Status:
Published