Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci
| العنوان: | Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci |
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| المؤلفون: | Maja Barbalić, Paul M. Ridker, Alex Parker, Daniel I. Chasman, Joshua C. Bis, Dov Shiffman, Guillaume Paré, Josée Dupuis, Emelia J. Benjamin, Lynda M. Rose, Abbas Dehghan |
| المصدر: | PLoS Genetics, Vol 7, Iss 4, p e1001374 (2011) PLoS Genetics |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Cancer Research, medicine.medical_specialty, Multifactorial Inheritance, Genotype, lcsh:QH426-470, Transcription Factor RelA, Cardiovascular Disorders/Coronary Artery Disease, Genome-wide association study, ICAM-1, GWAS, Disease, Biology, Genetics and Genomics/Complex Traits, Polymorphism, Single Nucleotide, ABO Blood-Group System, Cohort Studies, Gene Frequency, Molecular genetics, ABO blood group system, Genetics, medicine, Humans, Molecular Biology, Allele frequency, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Genetic association, Adaptor Proteins, Signal Transducing, Models, Genetic, Genome, Human, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Proteins, Lipase, Intercellular Adhesion Molecule-1, I-kappa B Kinase, lcsh:Genetics, Genetic Loci, Female, Immunology/Genetics of the Immune System, Genome-Wide Association Study, Research Article |
| الوصف: | 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. Author Summary Soluble Intercellular Adhesion Molecule 1 (sICAM-1) is an inflammatory marker that has been associated with several common diseases such as diabetes, heart disease, stroke, and malaria. While it is known that blood concentrations of sICAM-1 are at least partially genetically determined, our current knowledge of which genes mediate this effect is limited. Taking advantage of technologies allowing us to interrogate genetic variation on a whole-genome basis, we found that variation in the NFKBIK, PNPLA3, RELA, and SH2B3 genes are important determinant of sICAM-1 blood concentrations. The NFKBIB and RELA genes are involved in regulation of inflammation. These observations are significant because this is the first report of genetic association within these extensively studied inflammation genes. The PNPLA3 gene has previously been associated with liver disease, and the SH2B3 gene has been associated with a multitude of traits including cardiovascular disease. Extension of these associations to sICAM-1 adds to the intriguing diversity of effects of these genes. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4090913610b8ae5bcd0a11f9598490bTest https://doi.org/10.1371/journal.pgen.1001374Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a4090913610b8ae5bcd0a11f9598490b |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |