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C-reactive protein and its role in metabolic syndrome: mendelian randomisation study

Circulating C-reactive protein (CRP) is associated with the metabolic syndrome and might be causally linked to it. Our aim was to generate estimates of the association between plasma CRP and metabolic syndrome phenotypes that were free from confounding and reverse causation, to assess the causal rol... Full description

Journal Title: The Lancet (British edition) 2005, Vol.366 (9501), p.1954-1959
Main Author: Timpson, Nicholas J
Other Authors: Lawlor, Debbie A , Harbord, Roger M , Gaunt, Tom R , Day, Ian NM , Palmer, Lyle J , Hattersley, Andrew T , Ebrahim, Shah , Lowe, Gordon DO , Rumley, Ann , Smith, George Davey
Format: Electronic Article Electronic Article
Language: English
Subjects:
Hip
Quelle: Alma/SFX Local Collection
Publisher: England: Elsevier Ltd
ID: ISSN: 0140-6736
Link: https://www.ncbi.nlm.nih.gov/pubmed/16325697
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title: C-reactive protein and its role in metabolic syndrome: mendelian randomisation study
format: Article
creator:
  • Timpson, Nicholas J
  • Lawlor, Debbie A
  • Harbord, Roger M
  • Gaunt, Tom R
  • Day, Ian NM
  • Palmer, Lyle J
  • Hattersley, Andrew T
  • Ebrahim, Shah
  • Lowe, Gordon DO
  • Rumley, Ann
  • Smith, George Davey
subjects:
  • Abridged Index Medicus
  • Aged
  • Analysis
  • Blood cholesterol
  • Blood Pressure
  • Body mass
  • C-reactive protein
  • C-Reactive Protein - genetics
  • C-Reactive Protein - metabolism
  • Cardiovascular disease
  • Causality
  • Causation
  • Causes of
  • Cholesterol
  • Cholesterol - blood
  • Cytokines
  • Estimates
  • Female
  • Genetic aspects
  • Genetic research
  • Genetics
  • Genotype & phenotype
  • Haplotypes
  • Heart
  • High density lipoprotein
  • Hip
  • Humans
  • Insulin
  • Insulin resistance
  • Linear Models
  • Medical disorders
  • Medical research
  • Medicine, Experimental
  • Metabolic disorders
  • Metabolic syndrome
  • Metabolic Syndrome - blood
  • Metabolic Syndrome - genetics
  • Metabolic syndrome X
  • Metabolism
  • Middle Aged
  • Obesity
  • Phenotype
  • Phenotypes
  • Plasma
  • Proteins
  • Randomization
  • Regression analysis
  • Socioeconomic factors
  • Triglycerides
  • Triglycerides - blood
  • Variables
  • Womens health
ispartof: The Lancet (British edition), 2005, Vol.366 (9501), p.1954-1959
description: Circulating C-reactive protein (CRP) is associated with the metabolic syndrome and might be causally linked to it. Our aim was to generate estimates of the association between plasma CRP and metabolic syndrome phenotypes that were free from confounding and reverse causation, to assess the causal role of this protein. We examined associations between serum CRP concentration and metabolic syndrome phenotypes in the British Women's Heart and Health Study. We then compared these estimates with those derived from a mendelian randomised framework with common CRP gene haplotypes to generate unconfounded and unbiased estimates of any causal associations. In a sample of British women, body-mass index (BMI), systolic blood pressure, waist-to-hip ratio, serum concentrations of HDL cholesterol and triglycerides, and insulin resistance were all associated with plasma CRP concentration. CRP haplotypes were associated with plasma CRP concentration (p
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
url: Link


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titleC-reactive protein and its role in metabolic syndrome: mendelian randomisation study
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creatorTimpson, Nicholas J ; Lawlor, Debbie A ; Harbord, Roger M ; Gaunt, Tom R ; Day, Ian NM ; Palmer, Lyle J ; Hattersley, Andrew T ; Ebrahim, Shah ; Lowe, Gordon DO ; Rumley, Ann ; Smith, George Davey
creatorcontribTimpson, Nicholas J ; Lawlor, Debbie A ; Harbord, Roger M ; Gaunt, Tom R ; Day, Ian NM ; Palmer, Lyle J ; Hattersley, Andrew T ; Ebrahim, Shah ; Lowe, Gordon DO ; Rumley, Ann ; Smith, George Davey
descriptionCirculating C-reactive protein (CRP) is associated with the metabolic syndrome and might be causally linked to it. Our aim was to generate estimates of the association between plasma CRP and metabolic syndrome phenotypes that were free from confounding and reverse causation, to assess the causal role of this protein. We examined associations between serum CRP concentration and metabolic syndrome phenotypes in the British Women's Heart and Health Study. We then compared these estimates with those derived from a mendelian randomised framework with common CRP gene haplotypes to generate unconfounded and unbiased estimates of any causal associations. In a sample of British women, body-mass index (BMI), systolic blood pressure, waist-to-hip ratio, serum concentrations of HDL cholesterol and triglycerides, and insulin resistance were all associated with plasma CRP concentration. CRP haplotypes were associated with plasma CRP concentration (p<0·0001). With instrumental variable analyses, there was no association between plasma CRP concentration and any of the metabolic syndrome phenotypes analysed. There was strong evidence that linear regression and mendelian randomisation based estimation gave conflicting results for the CRP–BMI association (p=0·0002), and some evidence of conflicting results for the association of CRP with the score for insulin resistance (p=0·0139), triglycerides (p=0·0313), and HDL cholesterol (p=0·0688). Disparity between estimates of the association between plasma CRP and phenotypes comprising the metabolic syndrome derived from conventional analyses and those from a mendelian randomisation approach suggests that there is no causal association between CRP and the metabolic syndrome phenotypes.
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subjectAbridged Index Medicus ; Aged ; Analysis ; Blood cholesterol ; Blood Pressure ; Body mass ; C-reactive protein ; C-Reactive Protein - genetics ; C-Reactive Protein - metabolism ; Cardiovascular disease ; Causality ; Causation ; Causes of ; Cholesterol ; Cholesterol - blood ; Cytokines ; Estimates ; Female ; Genetic aspects ; Genetic research ; Genetics ; Genotype & phenotype ; Haplotypes ; Heart ; High density lipoprotein ; Hip ; Humans ; Insulin ; Insulin resistance ; Linear Models ; Medical disorders ; Medical research ; Medicine, Experimental ; Metabolic disorders ; Metabolic syndrome ; Metabolic Syndrome - blood ; Metabolic Syndrome - genetics ; Metabolic syndrome X ; Metabolism ; Middle Aged ; Obesity ; Phenotype ; Phenotypes ; Plasma ; Proteins ; Randomization ; Regression analysis ; Socioeconomic factors ; Triglycerides ; Triglycerides - blood ; Variables ; Womens health
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7Ebrahim, Shah
8Lowe, Gordon DO
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10Smith, George Davey
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descriptionCirculating C-reactive protein (CRP) is associated with the metabolic syndrome and might be causally linked to it. Our aim was to generate estimates of the association between plasma CRP and metabolic syndrome phenotypes that were free from confounding and reverse causation, to assess the causal role of this protein. We examined associations between serum CRP concentration and metabolic syndrome phenotypes in the British Women's Heart and Health Study. We then compared these estimates with those derived from a mendelian randomised framework with common CRP gene haplotypes to generate unconfounded and unbiased estimates of any causal associations. In a sample of British women, body-mass index (BMI), systolic blood pressure, waist-to-hip ratio, serum concentrations of HDL cholesterol and triglycerides, and insulin resistance were all associated with plasma CRP concentration. CRP haplotypes were associated with plasma CRP concentration (p<0·0001). With instrumental variable analyses, there was no association between plasma CRP concentration and any of the metabolic syndrome phenotypes analysed. There was strong evidence that linear regression and mendelian randomisation based estimation gave conflicting results for the CRP–BMI association (p=0·0002), and some evidence of conflicting results for the association of CRP with the score for insulin resistance (p=0·0139), triglycerides (p=0·0313), and HDL cholesterol (p=0·0688). Disparity between estimates of the association between plasma CRP and phenotypes comprising the metabolic syndrome derived from conventional analyses and those from a mendelian randomisation approach suggests that there is no causal association between CRP and the metabolic syndrome phenotypes.
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29Linear Models
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37Metabolic syndrome X
38Metabolism
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40Obesity
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42Phenotypes
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44Proteins
45Randomization
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47Socioeconomic factors
48Triglycerides
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50Variables
51Womens health
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abstractCirculating C-reactive protein (CRP) is associated with the metabolic syndrome and might be causally linked to it. Our aim was to generate estimates of the association between plasma CRP and metabolic syndrome phenotypes that were free from confounding and reverse causation, to assess the causal role of this protein. We examined associations between serum CRP concentration and metabolic syndrome phenotypes in the British Women's Heart and Health Study. We then compared these estimates with those derived from a mendelian randomised framework with common CRP gene haplotypes to generate unconfounded and unbiased estimates of any causal associations. In a sample of British women, body-mass index (BMI), systolic blood pressure, waist-to-hip ratio, serum concentrations of HDL cholesterol and triglycerides, and insulin resistance were all associated with plasma CRP concentration. CRP haplotypes were associated with plasma CRP concentration (p<0·0001). With instrumental variable analyses, there was no association between plasma CRP concentration and any of the metabolic syndrome phenotypes analysed. There was strong evidence that linear regression and mendelian randomisation based estimation gave conflicting results for the CRP–BMI association (p=0·0002), and some evidence of conflicting results for the association of CRP with the score for insulin resistance (p=0·0139), triglycerides (p=0·0313), and HDL cholesterol (p=0·0688). Disparity between estimates of the association between plasma CRP and phenotypes comprising the metabolic syndrome derived from conventional analyses and those from a mendelian randomisation approach suggests that there is no causal association between CRP and the metabolic syndrome phenotypes.
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pmid16325697
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