The relation of genetic and environmental factors to systemic inflammatory biomarker concentrations
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The relation of genetic and environmental factors to systemic inflammatory biomarker concentrations. / Schnabel, Renate B; Lunetta, Kathryn L; Larson, Martin G; Dupuis, Josée; Lipinska, Izabella; Rong, Jian; Chen, Ming-Huei; Zhao, Zhenming; Yamamoto, Jennifer F; Meigs, James B; Nicaud, Viviane; Perret, Claire; Zeller, Tanja; Blankenberg, Stefan; Tiret, Laurence; Keaney, John F; Vasan, Ramachandran S; Benjamin, Emelia J.
in: CIRC-CARDIOVASC GENE, Jahrgang 2, Nr. 3, 06.2009, S. 229-37.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The relation of genetic and environmental factors to systemic inflammatory biomarker concentrations
AU - Schnabel, Renate B
AU - Lunetta, Kathryn L
AU - Larson, Martin G
AU - Dupuis, Josée
AU - Lipinska, Izabella
AU - Rong, Jian
AU - Chen, Ming-Huei
AU - Zhao, Zhenming
AU - Yamamoto, Jennifer F
AU - Meigs, James B
AU - Nicaud, Viviane
AU - Perret, Claire
AU - Zeller, Tanja
AU - Blankenberg, Stefan
AU - Tiret, Laurence
AU - Keaney, John F
AU - Vasan, Ramachandran S
AU - Benjamin, Emelia J
PY - 2009/6
Y1 - 2009/6
N2 - BACKGROUND: Environmental and genetic correlates of inflammatory marker variability are incompletely understood. In the family-based Framingham Heart Study, we investigated heritability and candidate gene associations of systemic inflammatory biomarkers.METHODS AND RESULTS: In offspring participants (n=3710), we examined 11 inflammatory biomarkers (CD40 ligand, C-reactive protein, intercellular adhesion molecule-1, interleukin-6, urinary isoprostanes, monocyte chemoattractant protein-1, myeloperoxidase, P-selectin, tumor necrosis factor-alpha, tumor necrosis factor receptor II, fibrinogen). Heritability and bivariate genetic and environmental correlations were assessed by Sequential Oligogenic Linkage Analysis routines in 1012 family members. We examined 1943 tagging single-nucleotide polymorphisms in 233 inflammatory pathway genes with >or=5 minor allele carriers using a general genetic linear model. Clinical correlates explained 2.4% (CD40 ligand) to 28.5% (C-reactive protein) of the variability in inflammatory biomarkers. Estimated heritability ranged from 10.9% (isoprostanes) to 44.8% (P-selectin). Most correlations between biomarkers were weak although statistically significant. A total of 45 single-nucleotide polymorphism-biomarker associations met the q-value threshold of 0.25. Novel top single-nucleotide polymorphisms were observed in ICAM1 gene in relation to intercellular adhesion molecule-1 concentrations (rs1799969, P=1.32 x 10(-8)) and MPO in relation to myeloperoxidase (rs28730837, P=1.9 x 10(-5)). Lowest P values for trans-acting single-nucleotide polymorphisms were observed for APCS with monocyte chemoattractant protein-1 concentrations (rs1374486, P=1.01 x 10(-7)) and confirmed for IL6R with interleukin-6 concentrations (rs8192284, P=3.36 x 10(-5)). Novel potential candidates (APCS, MPO) need to be replicated.CONCLUSIONS: Our community-based data support the relevance of clinical and genetic factors for explaining variation in inflammatory biomarker traits.
AB - BACKGROUND: Environmental and genetic correlates of inflammatory marker variability are incompletely understood. In the family-based Framingham Heart Study, we investigated heritability and candidate gene associations of systemic inflammatory biomarkers.METHODS AND RESULTS: In offspring participants (n=3710), we examined 11 inflammatory biomarkers (CD40 ligand, C-reactive protein, intercellular adhesion molecule-1, interleukin-6, urinary isoprostanes, monocyte chemoattractant protein-1, myeloperoxidase, P-selectin, tumor necrosis factor-alpha, tumor necrosis factor receptor II, fibrinogen). Heritability and bivariate genetic and environmental correlations were assessed by Sequential Oligogenic Linkage Analysis routines in 1012 family members. We examined 1943 tagging single-nucleotide polymorphisms in 233 inflammatory pathway genes with >or=5 minor allele carriers using a general genetic linear model. Clinical correlates explained 2.4% (CD40 ligand) to 28.5% (C-reactive protein) of the variability in inflammatory biomarkers. Estimated heritability ranged from 10.9% (isoprostanes) to 44.8% (P-selectin). Most correlations between biomarkers were weak although statistically significant. A total of 45 single-nucleotide polymorphism-biomarker associations met the q-value threshold of 0.25. Novel top single-nucleotide polymorphisms were observed in ICAM1 gene in relation to intercellular adhesion molecule-1 concentrations (rs1799969, P=1.32 x 10(-8)) and MPO in relation to myeloperoxidase (rs28730837, P=1.9 x 10(-5)). Lowest P values for trans-acting single-nucleotide polymorphisms were observed for APCS with monocyte chemoattractant protein-1 concentrations (rs1374486, P=1.01 x 10(-7)) and confirmed for IL6R with interleukin-6 concentrations (rs8192284, P=3.36 x 10(-5)). Novel potential candidates (APCS, MPO) need to be replicated.CONCLUSIONS: Our community-based data support the relevance of clinical and genetic factors for explaining variation in inflammatory biomarker traits.
KW - Alleles
KW - Biomarkers/analysis
KW - Cohort Studies
KW - Community-Based Participatory Research
KW - Gene Frequency
KW - Humans
KW - Inflammation/genetics
KW - Inflammation Mediators/analysis
KW - Multivariate Analysis
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
U2 - 10.1161/CIRCGENETICS.108.804245
DO - 10.1161/CIRCGENETICS.108.804245
M3 - SCORING: Journal article
C2 - 20031590
VL - 2
SP - 229
EP - 237
JO - CIRC-CARDIOVASC GENE
JF - CIRC-CARDIOVASC GENE
SN - 1942-325X
IS - 3
ER -