Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci
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- Genome-wide association study of circulating interleukin 6 levels identifies novel loci
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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.
Originalsprog | Engelsk |
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Tidsskrift | Human Molecular Genetics |
Vol/bind | 30 |
Udgave nummer | 5 |
Sider (fra-til) | 393–409 |
ISSN | 0964-6906 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
© The Author(s) 2021. Published by Oxford University Press.
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