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

T.S. Ahluwalia; B.P. Prins; M. Abdollahi; N.J. Armstrong; S. Aslibekyan; L. Bain; B. Jefferis; J. Baumert; M. Beekman; Y. Ben-Shlomo; J.C. Bis; B.D. Mitchell; E. de Geus; G.E. Delgado; D. Marek; J. Eriksson; E. Kajantie; S. Kanoni; J.P. Kemp; C. Lu; R.E. Marioni; S. McLachlan; Y. Milaneschi; I.M. Nolte; A.M. Petrelis; E. Porcu; M. Sabater-Lleal; E. Naderi; I. Seppälä; T. Shah; G. Singhal; M. Standl; A. Teumer; A. Thalamuthu; E. Thiering; S. Trompet; C.M. Ballantyne; E.J. Benjamin; J.P. Casas; C. Toben; G. Dedoussis; J. Deelen; P. Durda; J. Engmann; M.F. Feitosa; H. Grallert; A. Hammarstedt; S.E. Harris; G. Homuth; J-J Hottenga; S. Jalkanen; Y. Jamshidi; M.C. Jawahar; T. Jess; M. Kivimäki; M.E. Kleber; J. Lahti; Y. Liu; P. Marques-Vidal; D. Mellström; S.P. Mooijaart; M. Müller-Nurasyid; B. Penninx; J.A. Revez; P. Rossing; K. Räikkönen; N. Sattar; H. Scharnagl; B. Sennblad; A. Silveira; B.S. Pourcain; N.J. Timpson; J. Trollor; J. van Dongen; D. Van Heemst; S. Visvikis-Siest; P. Vollenweider; U. Völker; M. Waldenberger; G. Willemsen; D. Zabaneh; R.W. Morris; D.K. Arnett; B.T. Baune; D.I. Boomsma; Y-P.C. Chang; I.J. Deary; P. Deloukas; J.G. Eriksson; D.M. Evans; M.A. Ferreira; T. Gaunt; V. Gudnason; A. Hamsten; J. Heinrich; A. Hingorani; S.E. Humphries; J.W. Jukema; W. Koenig; M. Kumari; Z. Kutalik; D.A. Lawlor; T. Lehtimäki; W. März; K.A. Mather; S. Naitza; M. Nauck; C. Ohlsson; J.F. Price; O. Raitakari; K. Rice; P.S. Sachdev; E. Slagboom; T.I.A. Sørensen; T. Spector; D. Stacey; M.G. Stathopoulou; T. Tanaka; S.G. Wannamethee; P. Whincup; J.I. Rotter; A. Dehghan; E. Boerwinkle; B.M. Psaty; H. Snieder; B.Z. Alizadeh

doi:10.1093/hmg/ddab023

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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

T.S. Ahluwalia, B.P. Prins, M. Abdollahi, N.J. Armstrong, S. Aslibekyan, L. Bain, B. Jefferis, J. Baumert, M. Beekman, Y. Ben-Shlomo, …

Human Molecular Genetics, Vol.30(5), pp.393-409

2021

DOI: https://doi.org/10.1093/hmg/ddab023

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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 (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.

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Title: Genome-wide association study of circulating interleukin 6 levels identifies novel loci
Authors/Creators: T.S. Ahluwalia (Author/Creator) - University of Copenhagen
B.P. Prins (Author/Creator) - University Medical Center Groningen
M. Abdollahi (Author/Creator) - University Medical Center Groningen
N.J. Armstrong (Author/Creator) - Murdoch University
S. Aslibekyan (Author/Creator) - University of Alabama at Birmingham
L. Bain (Author/Creator) - QIMR Berghofer Medical Research Institute
B. Jefferis (Author/Creator) - University College London
J. Baumert (Author/Creator)
M. Beekman (Author/Creator) - Leiden University Medical Center
Y. Ben-Shlomo (Author/Creator) - University of Bristol
J.C. Bis (Author/Creator) - University of Washington
B.D. Mitchell (Author/Creator) - University of Maryland, Baltimore
E. de Geus (Author/Creator)
G.E. Delgado (Author/Creator) - Heidelberg University
D. Marek (Author/Creator) - SIB Swiss Institute of Bioinformatics
J. Eriksson (Author/Creator) - University of Gothenburg
E. Kajantie (Author/Creator) - National Institutes of Health
S. Kanoni (Author/Creator) - Queen Mary University of London
J.P. Kemp (Author/Creator) - University of Bristol
C. Lu (Author/Creator) - Boston University
R.E. Marioni (Author/Creator) - University of Edinburgh
S. McLachlan (Author/Creator) - University of Edinburgh
Y. Milaneschi (Author/Creator) - Vrije Universiteit Amsterdam
I.M. Nolte (Author/Creator) - University Medical Center Groningen
A.M. Petrelis (Author/Creator) - Université de Lorraine
E. Porcu (Author/Creator)
M. Sabater-Lleal (Author/Creator) - Karolinska Institutet
E. Naderi (Author/Creator) - University Medical Center Groningen
I. Seppälä (Author/Creator)
T. Shah (Author/Creator) - UCL Australia
G. Singhal (Author/Creator) - The University of Adelaide
M. Standl (Author/Creator)
A. Teumer (Author/Creator) - Universitätsmedizin Greifswald
A. Thalamuthu (Author/Creator) - UNSW Sydney
E. Thiering (Author/Creator) - Ludwig-Maximilians-Universität München
S. Trompet (Author/Creator) - Leiden University Medical Center
C.M. Ballantyne (Author/Creator) - Baylor College of Medicine
E.J. Benjamin (Author/Creator) - Boston University
J.P. Casas (Author/Creator) - VA Boston Healthcare System
C. Toben (Author/Creator) - The University of Adelaide
G. Dedoussis (Author/Creator) - Harokopio University of Athens
J. Deelen (Author/Creator) - Max Planck Society
P. Durda (Author/Creator) - University of Vermont
J. Engmann (Author/Creator) - University College London
M.F. Feitosa (Author/Creator) - Washington University in St. Louis
H. Grallert (Author/Creator)
A. Hammarstedt (Author/Creator) - University of Gothenburg
S.E. Harris (Author/Creator) - University of Edinburgh
G. Homuth (Author/Creator) - Universitätsmedizin Greifswald
J-J Hottenga (Author/Creator) - Public Health Research Institute
S. Jalkanen (Author/Creator) - University of Turku
Y. Jamshidi (Author/Creator) - St George's, University of London
M.C. Jawahar (Author/Creator) - The University of Adelaide
T. Jess (Author/Creator)
M. Kivimäki (Author/Creator) - University College London
M.E. Kleber (Author/Creator) - Heidelberg University
J. Lahti (Author/Creator) - University of Helsinki
Y. Liu (Author/Creator) - Wake Forest University
P. Marques-Vidal (Author/Creator) - University of Lausanne
D. Mellström (Author/Creator) - University of Gothenburg
S.P. Mooijaart (Author/Creator) - Leiden University Medical Center
M. Müller-Nurasyid (Author/Creator)
B. Penninx (Author/Creator)
J.A. Revez (Author/Creator) - QIMR Berghofer Medical Research Institute
P. Rossing (Author/Creator) - University of Copenhagen
K. Räikkönen (Author/Creator) - University of Helsinki
N. Sattar (Author/Creator)
H. Scharnagl (Author/Creator) - Medical University of Graz
B. Sennblad (Author/Creator) - Karolinska Institutet
A. Silveira (Author/Creator) - Karolinska Institutet
B.S. Pourcain (Author/Creator) - University of Bristol
N.J. Timpson (Author/Creator) - University of Bristol
J. Trollor (Author/Creator) - UNSW Sydney
J. van Dongen (Author/Creator) - Public Health Research Institute
D. Van Heemst (Author/Creator) - Baylor College of Medicine
S. Visvikis-Siest (Author/Creator) - Université de Lorraine
P. Vollenweider (Author/Creator) - University of Lausanne
U. Völker (Author/Creator) - University of Turku
M. Waldenberger (Author/Creator)
G. Willemsen (Author/Creator) - Public Health Research Institute
D. Zabaneh (Author/Creator) - University College London
R.W. Morris (Author/Creator) - University of Bristol
D.K. Arnett (Author/Creator) - University of Kentucky
B.T. Baune (Author/Creator) - University of Münster
D.I. Boomsma (Author/Creator) - Public Health Research Institute
Y-P.C. Chang (Author/Creator) - University of Maryland, Baltimore
I.J. Deary (Author/Creator) - University of Edinburgh
P. Deloukas (Author/Creator) - Queen Mary University of London
J.G. Eriksson (Author/Creator) - University of Gothenburg
D.M. Evans (Author/Creator) - University of Bristol
M.A. Ferreira (Author/Creator) - QIMR Berghofer Medical Research Institute
T. Gaunt (Author/Creator) - University of Bristol
V. Gudnason (Author/Creator) - University of Iceland
A. Hamsten (Author/Creator) - Karolinska Institutet
J. Heinrich (Author/Creator) - Ludwig-Maximilians-Universität München
A. Hingorani (Author/Creator) - University College London
S.E. Humphries (Author/Creator) - University College London
J.W. Jukema (Author/Creator) - Leiden University Medical Center
W. Koenig (Author/Creator) - Technical University of Munich
M. Kumari (Author/Creator) - University College London
Z. Kutalik (Author/Creator) - SIB Swiss Institute of Bioinformatics
D.A. Lawlor (Author/Creator) - University of Bristol
T. Lehtimäki (Author/Creator)
W. März (Author/Creator) - Medical University of Graz
K.A. Mather (Author/Creator) - UNSW Sydney
S. Naitza (Author/Creator)
M. Nauck (Author/Creator) - Universitätsmedizin Greifswald
C. Ohlsson (Author/Creator) - University of Gothenburg
J.F. Price (Author/Creator) - University of Edinburgh
O. Raitakari (Author/Creator) - University of Turku
K. Rice (Author/Creator) - University of Washington
P.S. Sachdev (Author/Creator) - UNSW Sydney
E. Slagboom (Author/Creator) - Max Planck Society
T.I.A. Sørensen (Author/Creator) - University of Copenhagen
T. Spector (Author/Creator) - King's College London
D. Stacey (Author/Creator) - University of Cambridge
M.G. Stathopoulou (Author/Creator) - Université de Lorraine
T. Tanaka (Author/Creator) - National Institutes of Health
S.G. Wannamethee (Author/Creator) - University College London
P. Whincup (Author/Creator) - St George's, University of London
J.I. Rotter (Author/Creator) - The Lundquist Institute
A. Dehghan (Author/Creator) - Erasmus University Rotterdam
E. Boerwinkle (Author/Creator) - Baylor College of Medicine
B.M. Psaty (Author/Creator) - University of Washington
H. Snieder (Author/Creator) - University Medical Center Groningen
B.Z. Alizadeh (Author/Creator) - University Medical Center Groningen
Publication Details: Human Molecular Genetics, Vol.30(5), pp.393-409
Publisher: Oxford University Press
Identifiers: 991005540103407891
Copyright: © 2021 The Authors.
Murdoch Affiliation: School of Mathematics, Statistics, Chemistry and Physics
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
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ESI research areas: Molecular Biology & Genetics