Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To compreh...

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Published in:PLoS genetics Vol. 7; no. 4; p. e1001374
Main Authors: Paré, Guillaume, Ridker, Paul M., Rose, Lynda, Barbalic, Maja, Dupuis, Josée, Dehghan, Abbas, Bis, Joshua C., Benjamin, Emelia J., Shiffman, Dov, Parker, Alexander N., Chasman, Daniel I.
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.04.2011
Public Library of Science (PLoS)
Subjects:
ABO Blood-Group System - genetics
Adaptor Proteins, Signal Transducing
Algorithms
Cardiovascular Disorders/Coronary Artery Disease
Cell adhesion molecules
Charitable foundations
Cohort Studies
Diagnosis
Disease
Epidemiology
Female
Gene Frequency
Genetic aspects
Genetic Loci
Genetics
Genetics and Genomics/Complex Traits
Genome, Human
Genome-Wide Association Study
Genomes
Genotype
Heart
Heart attack
Humans
I-kappa B Kinase - genetics
Immunology/Genetics of the Immune System
Intercellular Adhesion Molecule-1 - blood
Intercellular Adhesion Molecule-1 - genetics
Intracellular Signaling Peptides and Proteins
Lipase - genetics
Liver diseases
Membrane Proteins - genetics
Models, Genetic
Multifactorial Inheritance
Physiological aspects
Polymorphism, Single Nucleotide
Proteins - genetics
Single nucleotide polymorphisms
Stroke
Stroke (Disease)
Transcription Factor RelA - genetics
Womens health
United States
ISSN:1553-7404, 1553-7390, 1553-7404
Online Access:Get full text
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Summary:Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4 × 10(-9)), PNPLA3 (rs738409, P  =  5.8 × 10(-9)), RELA (rs1049728, P =  2.7 × 10(-16)), and SH2B3 (rs3184504, P =  2.9 × 10(-17)). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.
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Conceived and designed the experiments: GP PMR ANP DIC. Performed the experiments: GP ANP DIC. Analyzed the data: GP LR MB. Contributed reagents/materials/analysis tools: GP PMR MB JD AD JCB EJB DS ANP DIC. Wrote the paper: GP.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1001374