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Genome-Wide Association Study Identifies Variants at the IL18 -BCO2 Locus Associated With Interleukin-18 Levels

Year: 2010

Type: article

Study design: Observational Study

Abstract: OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes. We sought to identify the common genetic variants associated with IL-18 levels. METHODS AND RESULTS: We performed a 2-stage genome-wide association study among women of European ancestry from the Nurses' Health Study (NHS) and Women's Genome Health Study (WGHS). IL-18 levels were measured by ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1 x 10(-5) significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31 x 10(-8)). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance level (P<5 x 10(-8)). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P=0.0002 and 0.0006, respectively). The 2 SNPs together explained 2.9% of variation of plasma IL-18 levels. CONCLUSIONS: This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.

Source: Arteriosclerosis Thrombosis and Vascular Biology

DOI: 10.1161/atvbaha.109.199422

Authors: Meian He, Marilyn C. Cornelis, Peter Kraft, Rob M. van Dam, Qi Sun, Cathy C. Laurie, Daniel B. Mirel, Daniel I. Chasman, Paul M Ridker, David J. Hunter, Frank B. Hu, Lu Qi

Institutions: Broad Institute, Brigham and Women's Hospital, Harvard University, University of Washington, Wuhan Union Hospital, Huazhong University of Science and Technology, Massachusetts Institute of Technology

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental and Craniofacial Research

Awards: GWAS of Venous Thrombosis, G1338396984, A Multiethnic Genome-Wide Scan of Prostate Cancer, Genetic Markers of CHD in Type 2 Diabetes, Study of Addiction: Genetics and Environment, Genome-Wide Associations Environmental Interactions in the Lung Health Study, International Consortium to Identify Genes and Interactions Controlling Oral Clef, Genes and Environment Initiatives in Type 2 Diabetes, Biochemical and Genetic Markers of Type 2 Diabetes Risk, Genome-wide association studies of prematurity and its complications, Boston Nutrition Obesity Research Center, GWA for Gene-Environment Interaction Effects Influencing CHD, Dental Caries: Whole Genome Association and Gene x Environment Studies, Dietary and Hormonal Determinants of Cancer in Women, Genes and Environment Initiative in Glaucoma, GWA Mapping: Maternal Metabolism-Birth Weight Interactions, Genome Wide Association Coordinating Center, GWAS of longitudinal blood pressure profiles from young adulthood to middle-age, A Center for GEI Association Studies, JH/CIDR Genotyping for Genome-Wide Association Studies, Genetic Risk to Stroke in Smokers and Nonsmokers in Two Ethnic Groups, Prospective Studies of Diet and Cancer in Men and Women, G8267674335, G985071772

OpenAlex ID: W2078417023

FWCI: 4.313

Cites: 37

Cited by: 77

Related to: 10