title: Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci.
abstract: 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.
authors.affiliation: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. pareg@McMaster.ca
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Lynda
authors.initials: L
authors.lastname: Rose
authors.forename: Maja
authors.initials: M
authors.lastname: Barbalic
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Dov
authors.initials: D
authors.lastname: Shiffman
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Parker
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008049:Lipase / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008957:Models, Genetic; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D051996:Transcription Factor RelA / Q000235:genetics*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000017:ABO Blood-Group System; D048868:Adaptor Proteins, Signal Transducing; D051550:I-kappa B Kinase; D018799:Intercellular Adhesion Molecule-1; D047908:Intracellular Signaling Peptides and Proteins; D008049:Lipase; D008565:Membrane Proteins; D011506:Proteins; D051996:Transcription Factor RelA; C498143:RELA protein, human; C490778:SH2B3 protein, human; C496560:IKBKB protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent