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

TitleGenome-wide association study of circulating interleukin 6 levels identifies novel loci.
Publication TypeJournal Article
Year of Publication2021
AuthorsAhluwalia TS, Prins BP, Abdollahi M, et al.
Corporate AuthorsCHARGE Inflammation working group
JournalHum Mol Genet
Volume30
Issue5
Pagination393-409
Date Published2021 04 27
ISSN1460-2083
Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and 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.

DOI10.1093/hmg/ddab023
Alternate JournalHum Mol Genet
PubMed ID33517400
PubMed Central IDPMC8098112
Grant ListMR/R024227/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL120393 / HL / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
MC_UU_12013/4 / MRC_ / Medical Research Council / United Kingdom
MR/S011676/1 / MRC_ / Medical Research Council / United Kingdom