@article{1febf5df343e4c509c5b6fa2f90d10a6,
title = "Generalizing polygenic risk scores from Europeans to Hispanics/Latinos",
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{\textquoteright}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.",
keywords = "admixed populations, genetic diversity, linkage disequilibrium",
author = "Grinde, {Kelsey E.} and Qibin Qi and Thornton, {Timothy A.} and Simin Liu and Shadyab, {Aladdin H.} and Chan, {Kei Hang K.} and Reiner, {Alexander P.} and Tamar Sofer",
note = "Funding Information: National Institute on Deafness and Other Communication Disorders; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Neurological Disorders and Stroke; NIH Institution-Office of Dietary Supplements; National Human Genome Research Institute, Grant/Award Numbers: HG006292, HL129132, R01HG005827; U.S. Department of Health and Human Services; National Science Foundation, Grant/Award Number: DGE-1256082 Funding Information: The authors thank the staff and participants of HCHS/SOL for their important contributions. The Hispanic Community Health Study/Study of Latinos is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01‐HC‐65233), University of Miami (HHSN268201300004I/N01‐HC‐65234), Albert Einstein College of Medicine (HHSN268201300002I/N01‐HC‐65235), University of Illinois at Chicago (HHSN268201300003I/ N01‐HC‐65236, Northwestern University), and San Diego State University (HHSN268201300005I/N01‐HC‐65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, and NIH Institution‐Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Funding support for the “Epidemiology of putative genetic variants: The Women{\textquoteright}s Health Initiative” study is provided through the NHGRI grants HG006292 and HL129132. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN26820 1100003C, HHSN268201100004C, and HHSC27120110 0004C. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: https://www.whi.org/about/SitePages/Study/% 20Organization.aspx. T. S. was supported by the NHLBI (R01 HL120393‐03S1 and 1R35HL135818) and NHGRI (R01HG005827). K. G. was supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE‐1256082. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Funding Information: The authors thank the staff and participants of HCHS/SOL for their important contributions. The Hispanic Community Health Study/Study of Latinos is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01-HC-65233), University of Miami (HHSN268201300004I/N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I/N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I/N01-HC-65236, Northwestern University), and San Diego State University (HHSN268201300005I/N01-HC-65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, and NIH Institution-Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Funding support for the ?Epidemiology of putative genetic variants: The Women?s Health Initiative? study is provided through the NHGRI grants HG006292 and HL129132. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSC271201100004C. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: https://www.whi.org/about/SitePages/Study/%20Organization.aspx. T. S. was supported by the NHLBI (R01 HL120393-03S1 and 1R35HL135818) and NHGRI (R01HG005827). K. G. was supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1256082. Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",
year = "2019",
month = feb,
doi = "10.1002/gepi.22166",
language = "English (US)",
volume = "43",
pages = "50--62",
journal = "Genetic Epidemiology",
issn = "0741-0395",
publisher = "Wiley-Liss Inc.",
number = "1",
}