Generalizing polygenic risk scores from Europeans to Hispanics/Latinos

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 l...

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Vydáno v:	Genetic epidemiology Ročník 43; číslo 1; s. 50 - 62
Hlavní autoři:	Grinde, Kelsey E., Qi, Qibin, Thornton, Timothy A., Liu, Simin, Shadyab, Aladdin H., Chan, Kei Hang K., Reiner, Alexander P., Sofer, Tamar
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Wiley Subscription Services, Inc 01.02.2019
Témata:	admixed populations Alleles Blood pressure Computer Simulation Gene frequency genetic diversity Genome-wide association studies Genome-Wide Association Study Genomes Hispanic Americans Hispanic or Latino - genetics Humans Linkage disequilibrium Linkage Disequilibrium - genetics Models, Genetic Multifactorial Inheritance - genetics Polygenic inheritance Polymorphism, Single Nucleotide - genetics Population genetics Risk Factors Single-nucleotide polymorphism Studies White People - genetics genetic diversity admixed populations linkage disequilibrium
ISSN:	0741-0395, 1098-2272, 1098-2272
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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.
AbstractList	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. Polygenic risk scores (PRSs) are typically constructed as 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), the majority of which have been performed in large populations of European Ancestry (EA) individuals. While 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, use of EA GWASs for weight estimation was suboptimal. Using non-EA GWAS results to estimate weights improved results. 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. 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. 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.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.
Author	Shadyab, Aladdin H. Sofer, Tamar Qi, Qibin Thornton, Timothy A. Liu, Simin Grinde, Kelsey E. Chan, Kei Hang K. Reiner, Alexander P.
AuthorAffiliation	6 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 1 Department of Biostatistics, University of Washington, Seattle, WA, USA 3 Department of Epidemiology, Brown University, Providence, RI, USA 5 Departments of Biomedical Sciences and Electronic Engineering, City University of Hong Kong, HKSAR 2 Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA 4 Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA, USA 8 Department of Medicine, Harvard Medical School, Boston, MA, USA 7 Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA
AuthorAffiliation_xml	– name: 1 Department of Biostatistics, University of Washington, Seattle, WA, USA – name: 7 Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA – name: 2 Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA – name: 4 Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA, USA – name: 3 Department of Epidemiology, Brown University, Providence, RI, USA – name: 8 Department of Medicine, Harvard Medical School, Boston, MA, USA – name: 6 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA – name: 5 Departments of Biomedical Sciences and Electronic Engineering, City University of Hong Kong, HKSAR
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Snippet	Polygenic risk scores (PRSs) are weighted sums of risk allele counts of single‐nucleotide polymorphisms (SNPs) associated with a disease or trait. PRSs are... Polygenic risk scores (PRSs) are weighted sums of risk allele counts of single-nucleotide polymorphisms (SNPs) associated with a disease or trait. PRSs are... Polygenic risk scores (PRSs) are typically constructed as weighted sums of risk allele counts of single nucleotide polymorphisms (SNPs) associated with a...
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SubjectTerms	admixed populations Alleles Blood pressure Computer Simulation Gene frequency genetic diversity Genome-wide association studies Genome-Wide Association Study Genomes Hispanic Americans Hispanic or Latino - genetics Humans Linkage disequilibrium Linkage Disequilibrium - genetics Models, Genetic Multifactorial Inheritance - genetics Polygenic inheritance Polymorphism, Single Nucleotide - genetics Population genetics Risk Factors Single-nucleotide polymorphism Studies White People - genetics
Title	Generalizing polygenic risk scores from Europeans to Hispanics/Latinos
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