Genetic analysis of over half a million people characterises C-reactive protein loci

Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Resea...

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Veröffentlicht in:	Nature communications Jg. 13; H. 1; S. 2198 - 10
Hauptverfasser:	Said, Saredo, Pazoki, Raha, Karhunen, Ville, Võsa, Urmo, Ligthart, Symen, Bodinier, Barbara, Koskeridis, Fotios, Welsh, Paul, Alizadeh, Behrooz Z., Chasman, Daniel I., Sattar, Naveed, Chadeau-Hyam, Marc, Evangelou, Evangelos, Jarvelin, Marjo-Riitta, Elliott, Paul, Tzoulaki, Ioanna, Dehghan, Abbas
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 22.04.2022 Nature Publishing Group Nature Portfolio
Schlagworte:	45/43 631/114/1314 631/208/205/2138 631/250/256/2515 Aging Airway management Biomarkers C-reactive protein C-Reactive Protein - genetics C-Reactive Protein - metabolism Chronic illnesses Clinical outcomes Epidemiology Gene expression Gene loci Genetic analysis Genetic Loci Genome-wide association studies Genome-Wide Association Study Humanities and Social Sciences Humans Inflammation Inflammation - genetics Male Mendelian Randomization Analysis Mental disorders multidisciplinary Phenomics Polymorphism, Single Nucleotide Prostate cancer Proteins Schizophrenia Science Science (multidisciplinary)
ISSN:	2041-1723, 2041-1723
Online-Zugang:	Volltext
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Abstract	Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels ( p ≤ 3.2 ×10 −6 ) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases. Inflammation is associated with a variety of diseases. Here, the authors identify 266 genetic loci associated with C-reactive protein levels, a marker of inflammation, in >500,000 Europeans, along with associated pathways, clinical outcomes and potential causal associations with disease.
AbstractList	Inflammation is associated with a variety of diseases. Here, the authors identify 266 genetic loci associated with C-reactive protein levels, a marker of inflammation, in >500,000 Europeans, along with associated pathways, clinical outcomes and potential causal associations with disease. Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels ( p ≤ 3.2 ×10 −6 ) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases. Inflammation is associated with a variety of diseases. Here, the authors identify 266 genetic loci associated with C-reactive protein levels, a marker of inflammation, in >500,000 Europeans, along with associated pathways, clinical outcomes and potential causal associations with disease. Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10−6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases. Inflammation is associated with a variety of diseases. Here, the authors identify 266 genetic loci associated with C-reactive protein levels, a marker of inflammation, in >500,000 Europeans, along with associated pathways, clinical outcomes and potential causal associations with disease. Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels ( p ≤ 3.2 ×10 −6 ) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases. Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10-6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10-6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases. Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10 ) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.
ArticleNumber	2198
Author	Pazoki, Raha Elliott, Paul Chasman, Daniel I. Sattar, Naveed Said, Saredo Võsa, Urmo Koskeridis, Fotios Evangelou, Evangelos Ligthart, Symen Welsh, Paul Tzoulaki, Ioanna Dehghan, Abbas Karhunen, Ville Jarvelin, Marjo-Riitta Alizadeh, Behrooz Z. Chadeau-Hyam, Marc Bodinier, Barbara
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/35459240$$D View this record in MEDLINE/PubMed
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Snippet	Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein... Inflammation is associated with a variety of diseases. Here, the authors identify 266 genetic loci associated with C-reactive protein levels, a marker of...
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SubjectTerms	45/43 631/114/1314 631/208/205/2138 631/250/256/2515 Aging Airway management Biomarkers C-reactive protein C-Reactive Protein - genetics C-Reactive Protein - metabolism Chronic illnesses Clinical outcomes Epidemiology Gene expression Gene loci Genetic analysis Genetic Loci Genome-wide association studies Genome-Wide Association Study Humanities and Social Sciences Humans Inflammation Inflammation - genetics Male Mendelian Randomization Analysis Mental disorders multidisciplinary Phenomics Polymorphism, Single Nucleotide Prostate cancer Proteins Schizophrenia Science Science (multidisciplinary)
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Title	Genetic analysis of over half a million people characterises C-reactive protein loci
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