Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Academic Article

Abstract

  • Interleukin 6 (IL-6) is a multifunctional cytokine with both pro-A nd anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Ahluwalia TS; Prins BP; Abdollahi M; Armstrong NJ; Aslibekyan S; Bain L; Jefferis B; Baumert J; Beekman M; Ben-Shlomo Y
  • Start Page

  • 393
  • End Page

  • 409
  • Volume

  • 30
  • Issue

  • 5