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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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 1×10-5 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31×10-8). 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<5×10-8). 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. Conclusion: This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.

Original languageEnglish (US)
Pages (from-to)885-890
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume30
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • GWA study
  • IL-18
  • IL18 gene

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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