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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_DFC20881CC51
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association study of circulating interleukin 6 levels identifies novel loci.
Journal
Human molecular genetics
Author(s)
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., Hottenga J.J., Jalkanen S., Jamshidi Y., Jawahar M.C., Jess T., Kivimaki M., Kleber M.E., Lahti J., Liu Y., Marques-Vidal P., Mellström D., Mooijaart S.P., Müller-Nurasyid M., Penninx B., Revez J.A., Rossing P., Räikkönen K., Sattar N., Scharnagl H., Sennblad B., Silveira A., Pourcain B.S., Timpson N.J., Trollor J., van Dongen J., Van Heemst D., Visvikis-Siest S., Vollenweider P., Völker U., Waldenberger M., Willemsen G., Zabaneh D., Morris R.W., Arnett D.K., Baune B.T., Boomsma D.I., Chang Y.C., Deary I.J., Deloukas P., Eriksson J.G., Evans D.M., Ferreira M.A., Gaunt T., Gudnason V., Hamsten A., Heinrich J., Hingorani A., Humphries S.E., Jukema J.W., Koenig W., Kumari M., Kutalik Z., Lawlor D.A., Lehtimäki T., März W., Mather K.A., Naitza S., Nauck M., Ohlsson C., Price J.F., Raitakari O., Rice K., Sachdev P.S., Slagboom E., Sørensen TIA, Spector T., Stacey D., Stathopoulou M.G., Tanaka T., Wannamethee S.G., Whincup P., Rotter J.I., Dehghan A., Boerwinkle E., Psaty B.M., Snieder H., Alizadeh B.Z.
Working group(s)
CHARGE Inflammation Working Group
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
27/04/2021
Peer-reviewed
Oui
Volume
30
Number
5
Pages
393-409
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
08/02/2021 14:08
Last modification date
12/01/2022 7:14
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