Approximate conditional phenotype analysis based on genome wide association summary statistics

Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder....

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Veröffentlicht in:Scientific reports Jg. 11; H. 1; S. 2518 - 13
Hauptverfasser: Wu, Peitao, Wang, Biqi, Lubitz, Steven A., Benjamin, Emelia J., Meigs, James B., Dupuis, Josée
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 28.01.2021
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Abstract Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.
AbstractList Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.
Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.
Abstract Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.
ArticleNumber 2518
Author Wang, Biqi
Meigs, James B.
Wu, Peitao
Dupuis, Josée
Lubitz, Steven A.
Benjamin, Emelia J.
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  surname: Wu
  fullname: Wu, Peitao
  organization: Department of Biostatistics, Boston University School of Public Health
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  surname: Wang
  fullname: Wang, Biqi
  organization: Department of Biostatistics, Boston University School of Public Health
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  givenname: Steven A.
  surname: Lubitz
  fullname: Lubitz, Steven A.
  organization: Cardiac Arrhythmia Service, Massachusetts General Hospital, The Broad Institute of Harvard and MIT
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  givenname: Emelia J.
  orcidid: 0000-0003-4076-2336
  surname: Benjamin
  fullname: Benjamin, Emelia J.
  organization: Cardiology and Preventive Medicine Sections, Evans Department of Medicine, Boston University School of Medicine, National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Department of Epidemiology, Boston University School of Public Health
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  givenname: James B.
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  givenname: Josée
  surname: Dupuis
  fullname: Dupuis, Josée
  email: dupuis@bu.edu
  organization: Department of Biostatistics, Boston University School of Public Health
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CitedBy_id crossref_primary_10_3389_fgene_2021_745901
crossref_primary_10_1186_s13040_024_00385_x
crossref_primary_10_1242_jeb_243411
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Snippet Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify...
Abstract Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to...
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SubjectTerms 631/114/2415
631/208/205/2138
Algorithms
Databases, Factual
Gene frequency
Genetic diversity
Genetic Predisposition to Disease
Genetic variance
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
Humanities and Social Sciences
Humans
Metabolic Syndrome - genetics
Metabolic Syndrome - metabolism
Models, Statistical
multidisciplinary
Phenotype
Phenotypes
Science
Science (multidisciplinary)
Statistical analysis
Statistics
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Title Approximate conditional phenotype analysis based on genome wide association summary statistics
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