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Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
by
Yao, Chen
, Courchesne, Paul
, Song, Ci
, Larson, Martin G.
, Hwang, Shih-Jen
, Maranville, Joseph C.
, Liu, Chunyu
, Keefe, Joshua
, Huan, Tianxiao
, Chen, George
, Laser, Annika
, Ho, Jennifer E.
, Runz, Heiko
, Lyass, Asya
, Levy, Daniel
, Mendelson, Michael
, Danesh, John
, Butterworth, Adam S.
, Wu, Hongsheng
, Graumann, Johannes
, Johnson, Andrew D.
, Suhre, Karsten
, Gieger, Christian
, Sun, Benjamin B.
in
38
/ 38/39
/ 38/43
/ 38/47
/ 38/61
/ 45
/ 45/43
/ 45/47
/ 45/61
/ 49
/ 631/208/457/649
/ 631/208/480
/ 631/45/612/1248
/ 692/4019/592/2727
/ Adult
/ Blood Proteins - genetics
/ Cardiovascular disease
/ Cardiovascular diseases
/ Cardiovascular Diseases - genetics
/ Cardiovascular Diseases - metabolism
/ Chromosome Mapping
/ Female
/ Gene Expression Profiling
/ Gene mapping
/ Genes
/ Genetic diversity
/ Genetic Predisposition to Disease - genetics
/ Genetic variance
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Genotype & phenotype
/ Heart diseases
/ Humanities and Social Sciences
/ Humans
/ Male
/ Middle Aged
/ multidisciplinary
/ Peptide mapping
/ Polymorphism, Single Nucleotide
/ Proteins
/ Quantitative trait loci
/ Quantitative Trait Loci - genetics
/ Randomization
/ Risk Factors
/ Science
/ Science (multidisciplinary)
/ Signal Transduction - genetics
/ Single-nucleotide polymorphism
/ Target recognition
2018
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Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
by
Yao, Chen
, Courchesne, Paul
, Song, Ci
, Larson, Martin G.
, Hwang, Shih-Jen
, Maranville, Joseph C.
, Liu, Chunyu
, Keefe, Joshua
, Huan, Tianxiao
, Chen, George
, Laser, Annika
, Ho, Jennifer E.
, Runz, Heiko
, Lyass, Asya
, Levy, Daniel
, Mendelson, Michael
, Danesh, John
, Butterworth, Adam S.
, Wu, Hongsheng
, Graumann, Johannes
, Johnson, Andrew D.
, Suhre, Karsten
, Gieger, Christian
, Sun, Benjamin B.
in
38
/ 38/39
/ 38/43
/ 38/47
/ 38/61
/ 45
/ 45/43
/ 45/47
/ 45/61
/ 49
/ 631/208/457/649
/ 631/208/480
/ 631/45/612/1248
/ 692/4019/592/2727
/ Adult
/ Blood Proteins - genetics
/ Cardiovascular disease
/ Cardiovascular diseases
/ Cardiovascular Diseases - genetics
/ Cardiovascular Diseases - metabolism
/ Chromosome Mapping
/ Female
/ Gene Expression Profiling
/ Gene mapping
/ Genes
/ Genetic diversity
/ Genetic Predisposition to Disease - genetics
/ Genetic variance
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Genotype & phenotype
/ Heart diseases
/ Humanities and Social Sciences
/ Humans
/ Male
/ Middle Aged
/ multidisciplinary
/ Peptide mapping
/ Polymorphism, Single Nucleotide
/ Proteins
/ Quantitative trait loci
/ Quantitative Trait Loci - genetics
/ Randomization
/ Risk Factors
/ Science
/ Science (multidisciplinary)
/ Signal Transduction - genetics
/ Single-nucleotide polymorphism
/ Target recognition
2018
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Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
by
Yao, Chen
, Courchesne, Paul
, Song, Ci
, Larson, Martin G.
, Hwang, Shih-Jen
, Maranville, Joseph C.
, Liu, Chunyu
, Keefe, Joshua
, Huan, Tianxiao
, Chen, George
, Laser, Annika
, Ho, Jennifer E.
, Runz, Heiko
, Lyass, Asya
, Levy, Daniel
, Mendelson, Michael
, Danesh, John
, Butterworth, Adam S.
, Wu, Hongsheng
, Graumann, Johannes
, Johnson, Andrew D.
, Suhre, Karsten
, Gieger, Christian
, Sun, Benjamin B.
in
38
/ 38/39
/ 38/43
/ 38/47
/ 38/61
/ 45
/ 45/43
/ 45/47
/ 45/61
/ 49
/ 631/208/457/649
/ 631/208/480
/ 631/45/612/1248
/ 692/4019/592/2727
/ Adult
/ Blood Proteins - genetics
/ Cardiovascular disease
/ Cardiovascular diseases
/ Cardiovascular Diseases - genetics
/ Cardiovascular Diseases - metabolism
/ Chromosome Mapping
/ Female
/ Gene Expression Profiling
/ Gene mapping
/ Genes
/ Genetic diversity
/ Genetic Predisposition to Disease - genetics
/ Genetic variance
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Genotype & phenotype
/ Heart diseases
/ Humanities and Social Sciences
/ Humans
/ Male
/ Middle Aged
/ multidisciplinary
/ Peptide mapping
/ Polymorphism, Single Nucleotide
/ Proteins
/ Quantitative trait loci
/ Quantitative Trait Loci - genetics
/ Randomization
/ Risk Factors
/ Science
/ Science (multidisciplinary)
/ Signal Transduction - genetics
/ Single-nucleotide polymorphism
/ Target recognition
2018
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Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
Journal Article
Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
2018
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Overview
Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome’s causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment.
Genetic variation can influence levels of disease-related plasma proteins and, thus, contribute to the pathogenesis of complex diseases. Here, the authors perform genome-wide QTL analysis for 71 plasma proteins to identify causal proteins for coronary heart disease and provide a molecular QTL browser.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/39
/ 38/43
/ 38/47
/ 38/61
/ 45
/ 45/43
/ 45/47
/ 45/61
/ 49
/ Adult
/ Cardiovascular Diseases - genetics
/ Cardiovascular Diseases - metabolism
/ Female
/ Genes
/ Genetic Predisposition to Disease - genetics
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Male
/ Polymorphism, Single Nucleotide
/ Proteins
/ Quantitative Trait Loci - genetics
/ Science
/ Signal Transduction - genetics
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