Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

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

Ahluwalia, T.S., Prins, B.P., Abdollahi, M., Armstrong, N.J.ORCID: 0000-0002-4477-293X, 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., Kivimäki, 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-P.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, T.I.A., 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. and Alizadeh, B.Z. (2021) Genome-wide association study of circulating interleukin 6 levels identifies novel loci. Human Molecular Genetics, 30 (5). pp. 393-409.

[img]
Preview
PDF - Published Version
Download (1MB) | Preview
Free to read: https://doi.org/10.1093/hmg/ddab023
*No subscription required

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.

Item Type: Journal Article
Murdoch Affiliation(s): Mathematics, Statistics, Chemistry and Physics
Publisher: Oxford University Press
Copyright: © 2021 The Authors.
URI: http://researchrepository.murdoch.edu.au/id/eprint/61007
Item Control Page Item Control Page

Downloads

Downloads per month over past year