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

Publication ,  Journal Article
Ahluwalia, TS; Prins, BP; Abdollahi, M; Armstrong, NJ; Aslibekyan, S; Bain, L; Jefferis, B; Baumert, J; Beekman, M; Ben-Shlomo, Y; Bis, JC ...
Published in: Hum Mol Genet
April 27, 2021

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.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

April 27, 2021

Volume

30

Issue

5

Start / End Page

393 / 409

Location

England

Related Subject Headings

  • White People
  • Receptors, Interleukin-6
  • Polymorphism, Single Nucleotide
  • Interleukin-6
  • Interleukin-1
  • Interleukin 1 Receptor Antagonist Protein
  • Humans
  • HLA-DRB1 Chains
  • Genome-Wide Association Study
  • Genetics & Heredity
 

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Ahluwalia, T. S., Prins, B. P., Abdollahi, M., Armstrong, N. J., Aslibekyan, S., Bain, L., … Alizadeh, B. Z. (2021). Genome-wide association study of circulating interleukin 6 levels identifies novel loci. Hum Mol Genet, 30(5), 393–409. https://doi.org/10.1093/hmg/ddab023
Ahluwalia, Tarunveer S., Bram P. Prins, Mohammadreza Abdollahi, Nicola J. Armstrong, Stella Aslibekyan, Lisa Bain, Barbara Jefferis, et al. “Genome-wide association study of circulating interleukin 6 levels identifies novel loci.Hum Mol Genet 30, no. 5 (April 27, 2021): 393–409. https://doi.org/10.1093/hmg/ddab023.
Ahluwalia TS, Prins BP, Abdollahi M, Armstrong NJ, Aslibekyan S, Bain L, et al. Genome-wide association study of circulating interleukin 6 levels identifies novel loci. Hum Mol Genet. 2021 Apr 27;30(5):393–409.
Ahluwalia, Tarunveer S., et al. “Genome-wide association study of circulating interleukin 6 levels identifies novel loci.Hum Mol Genet, vol. 30, no. 5, Apr. 2021, pp. 393–409. Pubmed, doi:10.1093/hmg/ddab023.
Ahluwalia TS, Prins BP, Abdollahi M, Armstrong NJ, Aslibekyan S, Bain L, Jefferis B, Baumert J, Beekman M, Ben-Shlomo Y, Bis JC, Mitchell BD, de Geus E, Delgado GE, Marek D, Eriksson J, Kajantie E, Kanoni S, Kemp JP, Lu C, Marioni RE, McLachlan S, Milaneschi Y, Nolte IM, Petrelis AM, Porcu E, Sabater-Lleal M, Naderi E, Seppälä I, Shah T, Singhal G, Standl M, Teumer A, Thalamuthu A, Thiering E, Trompet S, Ballantyne CM, Benjamin EJ, Casas JP, Toben C, Dedoussis G, Deelen J, Durda P, Engmann J, Feitosa MF, Grallert H, Hammarstedt A, Harris SE, Homuth G, Hottenga J-J, Jalkanen S, Jamshidi Y, Jawahar MC, Jess T, Kivimaki M, Kleber ME, Lahti J, Liu Y, Marques-Vidal P, Mellström D, Mooijaart SP, Müller-Nurasyid M, Penninx B, Revez JA, Rossing P, Räikkönen K, Sattar N, Scharnagl H, Sennblad B, Silveira A, Pourcain BS, Timpson NJ, 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 RW, Arnett DK, Baune BT, Boomsma DI, Chang Y-PC, Deary IJ, Deloukas P, Eriksson JG, Evans DM, Ferreira MA, Gaunt T, Gudnason V, Hamsten A, Heinrich J, Hingorani A, Humphries SE, Jukema JW, Koenig W, Kumari M, Kutalik Z, Lawlor DA, Lehtimäki T, März W, Mather KA, Naitza S, Nauck M, Ohlsson C, Price JF, Raitakari O, Rice K, Sachdev PS, Slagboom E, Sørensen TIA, Spector T, Stacey D, Stathopoulou MG, Tanaka T, Wannamethee SG, Whincup P, Rotter JI, Dehghan A, Boerwinkle E, Psaty BM, Snieder H, Alizadeh BZ. Genome-wide association study of circulating interleukin 6 levels identifies novel loci. Hum Mol Genet. 2021 Apr 27;30(5):393–409.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

April 27, 2021

Volume

30

Issue

5

Start / End Page

393 / 409

Location

England

Related Subject Headings

  • White People
  • Receptors, Interleukin-6
  • Polymorphism, Single Nucleotide
  • Interleukin-6
  • Interleukin-1
  • Interleukin 1 Receptor Antagonist Protein
  • Humans
  • HLA-DRB1 Chains
  • Genome-Wide Association Study
  • Genetics & Heredity