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Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci

Ahluwalia, TS; Prins, BP; Abdollahi, M; Armstrong, NJ; Aslibekyan, S; Bain, L; Jefferis, B; ... Alizadeh, BZ; + view all (2021) Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci. Human Molecular Genetics 10.1093/hmg/ddab023. (In press). Green open access

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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 (n{discovery} = 52 654 and n_{replication} = 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 (p_{combined} = 1.5 × 10^{−10}) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (p_{combined} = 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.

Type: Article
Title: Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/hmg/ddab023
Publisher version: https://doi.org/10.1093/hmg/ddab023
Language: English
Additional information: © The Author(s) 2021. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Primary Care and Population Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10120586
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