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

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

Title: Genome-wide association study of circulating interleukin 6 levels identifies novel loci
Author: Ahluwalia, Tarunveer S.
Prins, Bram P.
Abdollahi, Mohammadreza
Armstrong, Nicola J.
Aslibekyan, Stella
Bain, Lisa
Jefferis, Barbara
Baumert, Jens
Beekman, Marian
Ben-Shlomo, Yoav
... 40 more authors Show all authors
Date: 2021-01-30
Language: English
Scope: 17
Department: Faculty of Medicine
Series: Human Molecular Genetics; 30(5)
ISSN: 0964-6906
DOI: https://doi.org/10.1093/hmg/ddab023
Subject: Ónæmisfræði; Erfðafræði; Sameindalíffræði; Cohort Studies; Gene Expression Regulation; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA-DRB1 Chains/genetics; Humans; Interleukin 1 Receptor Antagonist Protein/genetics; Interleukin-1/genetics; Interleukin-6/blood; Polymorphism, Single Nucleotide; Receptors, Interleukin-6/genetics; Whites/genetics; Genetics (clinical); Genetics; Molecular Biology
URI: https://hdl.handle.net/20.500.11815/3131

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Citation:

Ahluwalia , T S , Prins , B P , Abdollahi , M , Armstrong , N J , Aslibekyan , S , Bain , L , Jefferis , B , Baumert , J , Beekman , M , Ben-Shlomo , Y , Bis , J C , Mitchell , B D , De Geus , E , Delgado , G E , Marek , D , Eriksson , J , Kajantie , E , Kanoni , S , Kemp , J P , Lu , C , Marioni , R E , McLachlan , S , Milaneschi , Y , Nolte , I M , Petrelis , A M , Porcu , E , Sabater-Lleal , M , Naderi , E , Seppälä , I , Shah , T , Singhal , G , Standl , M , Teumer , A , Thalamuthu , A , Thiering , E , Trompet , S , Ballantyne , C M , Benjamin , E J , Casas , J P , Toben , C , Dedoussis , G , Deelen , J , Durda , P , Engmann , J , Feitosa , M F , Grallert , H , Hammarstedt , A , Harris , S E , Homuth , G & Guðnason , V G 2021 , ' Genome-wide association study of circulating interleukin 6 levels identifies novel loci ' , Human Molecular Genetics , vol. 30 , no. 5 , pp. 393-409 . https://doi.org/10.1093/hmg/ddab023

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.

Description:

Funding Novo Nordisk Foundation (NNF18OC0052457 to T.S.A.). Detailed Funding statements from participating study cohorts can be found in Supplementary Material, Table S12. Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press.

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