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

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.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000A-FAD1-0 Version Permalink: https://hdl.handle.net/21.11116/0000-000A-FAD2-F

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https://www.ncbi.nlm.nih.gov/pubmed/33517400 (Any fulltext) Open Access status unknown

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Ahluwalia, T. S., Author
Prins, B. P., Author
Abdollahi, M., Author
Armstrong, N. J., Author
Aslibekyan, S., Author
Bain, L., Author
Jefferis, B., Author
Baumert, J., Author
Beekman, M., Author
Ben-Shlomo, Y., Author
Bis, J. C., Author
Mitchell, B. D., Author
de Geus, E., Author
Delgado, G. E., Author
Marek, D., Author
Eriksson, J., Author
Kajantie, E., Author
Kanoni, S., Author
Kemp, J. P., Author
Lu, C., Author
Marioni, R. E., AuthorMcLachlan, S., AuthorMilaneschi, Y., AuthorNolte, I. M., AuthorPetrelis, A. M., AuthorPorcu, E., AuthorSabater-Lleal, M., AuthorNaderi, E., AuthorSeppala, I., AuthorShah, T., AuthorSinghal, G., AuthorStandl, M., AuthorTeumer, A., AuthorThalamuthu, A., AuthorThiering, E., AuthorTrompet, S., AuthorBallantyne, C. M., AuthorBenjamin, E. J., AuthorCasas, J. P., AuthorToben, C., AuthorDedoussis, G., AuthorDeelen, J.¹, Author Durda, P., AuthorEngmann, J., AuthorFeitosa, M. F., AuthorGrallert, H., AuthorHammarstedt, A., AuthorHarris, S. E., AuthorHomuth, G., AuthorHottenga, J. J., AuthorJalkanen, S., AuthorJamshidi, Y., AuthorJawahar, M. C., AuthorJess, T., AuthorKivimaki, M., AuthorKleber, M. E., AuthorLahti, J., AuthorLiu, Y., AuthorMarques-Vidal, P., AuthorMellstrom, D., AuthorMooijaart, S. P., AuthorMuller-Nurasyid, M., AuthorPenninx, B., AuthorRevez, J. A., AuthorRossing, P., AuthorRaikkonen, K., AuthorSattar, N., AuthorScharnagl, H., AuthorSennblad, B., AuthorSilveira, A., AuthorPourcain, B. S., AuthorTimpson, N. J., AuthorTrollor, J., AuthorGroup, Charge Inflammation Working, Authorvan Dongen, J., AuthorVan Heemst, D., AuthorVisvikis-Siest, S., AuthorVollenweider, P., AuthorVolker, U., AuthorWaldenberger, M., AuthorWillemsen, G., AuthorZabaneh, D., AuthorMorris, R. W., AuthorArnett, D. K., AuthorBaune, B. T., AuthorBoomsma, D. I., AuthorChang, Y. C., AuthorDeary, I. J., AuthorDeloukas, P., AuthorEriksson, J. G., AuthorEvans, D. M., AuthorFerreira, M. A., AuthorGaunt, T., AuthorGudnason, V., AuthorHamsten, A., AuthorHeinrich, J., AuthorHingorani, A., AuthorHumphries, S. E., AuthorJukema, J. W., AuthorKoeing, W., AuthorKumari, M., AuthorKutalik, Z., AuthorLawlor, D. A., AuthorLehtimaki, T., AuthorMarz, W., AuthorMather, K., AuthorNaitza, S., AuthorNauck, M., AuthorOhlsson, C., AuthorPrice, J. F., AuthorRaitakari, O., AuthorRice, K., AuthorSachdev, P. S., AuthorSlagboom, P. E.², Author Sorensen, T. I. A., AuthorSpector, T., AuthorStacey, D., AuthorStathopoulou, M. G., AuthorTanaka, T., AuthorWannamethee, S. G., AuthorWhincup, P., AuthorRotter, J. I., AuthorDehghan, A., AuthorBoerwinkle, E., AuthorPsaty, B. M., AuthorSnieder, H., AuthorAlizadeh, B. Z., Author more..

Affiliations:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006
2Slagboom – Molecular Epidemiology, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394013

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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.

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Dates: Published Online: 2021-02-01Date issued: 2021-02-01

Publication Status: Issued

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Identifiers: Other: 33517400
DOI: 10.1093/hmg/ddab023
ISSN: 1460-2083 (Electronic)0964-6906 (Linking)

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Title: Hum Mol Genet

Source Genre: Journal

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Pages: - Volume / Issue: 5 (30) Sequence Number: - Start / End Page: 393 - 409 Identifier: -