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Generalizing polygenic risk scores from Europeans to Hispanics/Latinos.

TitleGeneralizing polygenic risk scores from Europeans to Hispanics/Latinos.
Publication TypePublication
Year2019
AuthorsGrinde KE, Qi Q, Thornton TA, Liu S, Shadyab AH, Chan KHang K, Reiner AP, Sofer T
JournalGenet Epidemiol
Volume43
Issue1
Pagination50-62
Date Published2019 02
ISSN1098-2272
KeywordsComputer Simulation, European Continental Ancestry Group, genome-wide association study, Hispanic Americans, Humans, Linkage Disequilibrium, Models, Genetic, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors
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.

DOI10.1002/gepi.22166
Alternate JournalGenet Epidemiol
PubMed ID30368908
PubMed Central IDPMC6330129
Grant ListHHSN268201300005C / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
/ MD / NIMHD NIH HHS / United States
HHSN268201300004C / HL / NHLBI 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
HHSN268201300001C / HL / NHLBI NIH HHS / United States
/ DE / NIDCR NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
HHSN268201300005I/N01-HC-65237 / NH / NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
R01 HL129132 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI 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
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
HHSN268201100002C / WH / WHI NIH HHS / United States
HHSN268201100004C / HL / NHLBI NIH HHS / United States
HHSN268201300003C / HG / NHGRI NIH HHS / United States
HHSN268201300004I/N01-HC-65234 / NH / NIH HHS / United States
T32 GM081062 / GM / NIGMS NIH HHS / United States
R01 HG005827 / HG / NHGRI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
R01HG005827 / HG / NHGRI NIH HHS / United States
HL129132 / HG / NHGRI NIH HHS / United States
HHSN268201100002C / HL / NHLBI NIH HHS / United States
HG006292 / HG / NHGRI NIH HHS / United States
/ DK / NIDDK NIH HHS / United States
HHSN268201300002I/N01-HC-65235 / NH / NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
MS#: 
0504
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
ECI: 
Manuscript Status: 
Published