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

Genome-Wide Association Study Identifies Variants at the IL18-BCO2 Locus Associated With... Genome-Wide Association Study Identifies Variants at the IL18-BCO2 Locus Associated With Interleukin-18 Levels 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 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, n1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 110 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P6.3110 ). 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 (P510 ). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P0.0002 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

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

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ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/ATVBAHA.109.199422
pmid
20150558

Abstract

Genome-Wide Association Study Identifies Variants at the IL18-BCO2 Locus Associated With Interleukin-18 Levels 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 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, n1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 110 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P6.3110 ). 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 (P510 ). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P0.0002

Journal

Arteriosclerosis, Thrombosis, and Vascular BiologyWolters Kluwer Health

Published: Apr 1, 2010

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