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. and 106 moreAhluwalia, 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., St Pourcain, B., Timpson, N. J., Trollor, J., CHARGE Inflammation Working Group, 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., & Alizadeh, B. Z.
(2021). Genome-wide association study of circulating interleukin 6 levels identifies novel loci.
Human Molecular Genetics, 5(1), 393-409. doi:10.1093/hmg/ddab023.
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.
Publication type
Journal article
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