title: Genetic and environmental influences on the prospective correlation between systemic inflammation and coronary heart disease death in male twins.
abstract: OBJECTIVE
  Because of lack of evidence, we aimed to examine to what degree low-grade systemic inflammation and coronary heart disease (CHD) death shared common genetic and environmental substrates.
  
  
  RESULTS
  From the 41-year prospective National Heart, Lung, and Blood Institute Twin Study, we included 950 middle-aged male twins at baseline (1969-1973). Low-grade systemic inflammation was measured with plasma levels of interleukin-6 (IL-6) and C-reactive protein. Univariate and bivariate structural equation models were used, adjusted for a risk score for CHD death. The score-adjusted heritability was 19% for IL-6, 27% for C-reactive protein, and 22% for CHD death. The positive phenotypic correlation of IL-6 with CHD death (radjusted=0.27; 95% confidence interval [CI], 0.08-0.43) was driven by additive genetic factors (contribution [relative contribution], 0.30 [111%]) but attenuated by unique environment (-0.03 [-11%]). The genetic correlation between IL-6 and CHD death was 0.74 (95% CI, 0.21-1.00), whereas the unique environmental correlation was -0.05 (95% CI, -0.35 to 0.25). The proportion of genetic variance for CHD death shared with that for IL-6 was 74%. The phenotypic correlation of C-reactive protein with CHD death (radjusted=0.10; 95% CI, -0.02 to 0.22) was explained by additive genetic factors (0.20 [149%]) but was attenuated by the unique environment (-0.09 [-49%]). The genetic correlation of C-reactive protein with CHD death was 0.63 (95% CI, -0.07 to 1.00), whereas the unique environmental correlation was -0.07 (95% CI, -0.29 to 0.17).
  
  
  CONCLUSIONS
  Low-grade systemic inflammation, measured by IL-6, and long-term CHD death share moderate genetic substrates that augment both traits.
authors.affiliation: From the Division of Epidemiology, Department of Medicine, Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN (S.-H.W., J.D.); Department of Psychiatry (M.C.N.) and Department of Human and Molecular Genetics (M.C.N.), Virginia Commonwealth University, Richmond; Division of Endocrinology (A.J.A., R.V.C.) and Department of Medical and Molecular Genetics (T.R.), Indiana University School of Medicine, Indianapolis; and Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA (R.E.K.).
authors.forename: Sheng-Hui
authors.initials: SH
authors.lastname: Wu
authors.affiliation: From the Division of Epidemiology, Department of Medicine, Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN (S.-H.W., J.D.); Department of Psychiatry (M.C.N.) and Department of Human and Molecular Genetics (M.C.N.), Virginia Commonwealth University, Richmond; Division of Endocrinology (A.J.A., R.V.C.) and Department of Medical and Molecular Genetics (T.R.), Indiana University School of Medicine, Indianapolis; and Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA (R.E.K.).
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.affiliation: From the Division of Epidemiology, Department of Medicine, Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN (S.-H.W., J.D.); Department of Psychiatry (M.C.N.) and Department of Human and Molecular Genetics (M.C.N.), Virginia Commonwealth University, Richmond; Division of Endocrinology (A.J.A., R.V.C.) and Department of Medical and Molecular Genetics (T.R.), Indiana University School of Medicine, Indianapolis; and Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA (R.E.K.).
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Acton
authors.affiliation: From the Division of Epidemiology, Department of Medicine, Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN (S.-H.W., J.D.); Department of Psychiatry (M.C.N.) and Department of Human and Molecular Genetics (M.C.N.), Virginia Commonwealth University, Richmond; Division of Endocrinology (A.J.A., R.V.C.) and Department of Medical and Molecular Genetics (T.R.), Indiana University School of Medicine, Indianapolis; and Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA (R.E.K.).
authors.forename: Robert V
authors.initials: RV
authors.lastname: Considine
authors.affiliation: From the Division of Epidemiology, Department of Medicine, Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN (S.-H.W., J.D.); Department of Psychiatry (M.C.N.) and Department of Human and Molecular Genetics (M.C.N.), Virginia Commonwealth University, Richmond; Division of Endocrinology (A.J.A., R.V.C.) and Department of Medical and Molecular Genetics (T.R.), Indiana University School of Medicine, Indianapolis; and Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA (R.E.K.).
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Krasnow
authors.affiliation: From the Division of Epidemiology, Department of Medicine, Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN (S.-H.W., J.D.); Department of Psychiatry (M.C.N.) and Department of Human and Molecular Genetics (M.C.N.), Virginia Commonwealth University, Richmond; Division of Endocrinology (A.J.A., R.V.C.) and Department of Medical and Molecular Genetics (T.R.), Indiana University School of Medicine, Indianapolis; and Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA (R.E.K.).
authors.forename: Terry
authors.initials: T
authors.lastname: Reed
authors.affiliation: From the Division of Epidemiology, Department of Medicine, Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN (S.-H.W., J.D.); Department of Psychiatry (M.C.N.) and Department of Human and Molecular Genetics (M.C.N.), Virginia Commonwealth University, Richmond; Division of Endocrinology (A.J.A., R.V.C.) and Department of Medical and Molecular Genetics (T.R.), Indiana University School of Medicine, Indianapolis; and Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA (R.E.K.). jun.dai@vanderbilt.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Dai
mesh_terms: D015415:Biomarkers; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D003327:Coronary Disease / Q000235:genetics* / Q000401:mortality; D004200:Diseases in Twins / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D008055:Lipids; D002097:C-Reactive Protein
keywords: C-reactive protein; coronary disease; genes; interleukin-6; mortality; twins
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