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

Ahluwalia, T.S.; Prins, B.P.; Abdollahi, M.; Armstrong, N.J.; Aslibekyan, S.; Bain, L.; ... ; CHARGE Inflammation Working Grp (2021)

Article / Letter to editor

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 67428 (n(discovery)=52654 and n(replication)=14774) 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, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

• All authors: 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.; Geus, E. de; 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.; Seppala, 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.; Mellstrom, D.; Mooijaart, S.P.; Muller-Nurasyid, M.; Penninx, B.; Revez, J.A.; Rossing, P.; Raikkonen, K.; Sattar, N.; Scharnagl, H.; Sennblad, B.; Silveira, A.; St Pourcain, B.; Timpson, N.J.; Trollor, J.; Dongen, J. van; Heemst, D. van; Visvikis-Siest, S.; Vollenweider, P.; Volker, 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.; Lehtimaki, T.; Marz, W.; Mather, K.A.; Naitza, S.; Nauck, M.; Ohlsson, C.; Price, J.F.; Raitakari, O.; Rice, K.; Sachdev, P.S.; Slagboom, E.; Sorensen, 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.; Alizadeh, B.Z.; CHARGE Inflammation Working Grp
• Date: 2021-03-01
• Journal: Human Molecular Genetics
• Volume: 30
• Issue: 5
• Pages: 393 - 409
• DOI: doi:10.1093/hmg/ddab023
• Link: https://academic.oup.com/hmg/article-pdf/30/5/393/37775647/ddab023.pdf