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.; 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.; 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.; Pourcain, B. S.; Timpson, N. J.; Trollor, J.; Group, Charge Inflammation Working; van Dongen, J.; Van Heemst, D.; 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. 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.; Koeing, W.; Kumari, M.; Kutalik, Z.; Lawlor, D. A.; Lehtimaki, T.; Marz, W.; Mather, K.; Naitza, S.; Nauck, M.; Ohlsson, C.; Price, J. F.; Raitakari, O.; Rice, K.; Sachdev, P. S.; Slagboom, P. 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.

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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Deelen, J.
Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Slagboom, P. E.
Slagboom – Molecular Epidemiology, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/33517400
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Citation

Ahluwalia, T. S., Prins, B. P., Abdollahi, M., Armstrong, N. J., Aslibekyan, S., Bain, L., et al. (2021). Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci. Hum Mol Genet, 5(30), 393-409. doi:10.1093/hmg/ddab023.

Cite as: https://hdl.handle.net/21.11116/0000-000A-FAD1-0

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