| Title: |
Genome-wide association study of circulating interleukin 6 levels identifies novel loci |
| Authors: |
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, JJ; 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; Raïkkönen, K; Sattar, N; Scharnagl, H; Sennblad, B; Silveira, A; Pourcain, BS; Timpson, NJ; Trollor, J; 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, YPC; 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; Sachdev, Perminder; Mather, Karen |
| Source: |
urn:ISSN:0964-6906 ; urn:ISSN:1460-2083 ; Human Molecular Genetics, 30, 5, 393-409 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2021 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
31 Biological Sciences; 3105 Genetics; Genetics; Human Genome; 2.1 Biological and endogenous factors; Inflammatory and immune system; Cohort Studies; Gene Expression Regulation; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA-DRB1 Chains; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-6; Polymorphism; Single Nucleotide; Receptors; White People; CHARGE Inflammation Working Group; anzsrc-for: 31 Biological Sciences; anzsrc-for: 3105 Genetics; anzsrc-for: 06 Biological Sciences; anzsrc-for: 11 Medical and Health Sciences |
| Description: |
Interleukin 6 (IL-6) is a multifunctional cytokine with both pro-A nd 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
http://purl.org/au-research/grants/nhmrc/APP1085619; http://purl.org/au-research/grants/nhmrc/APP1093083; http://purl.org/au-research/grants/nhmrc/APP1115462; http://purl.org/au-research/grants/nhmrc/APP1115575; http://purl.org/au-research/grants/nhmrc/APP1161858; https://hdl.handle.net/1959.4/unsworks_75486; https://doi.org/10.1093/hmg/ddab023 |
| DOI: |
10.1093/hmg/ddab023 |
| Availability: |
https://hdl.handle.net/1959.4/unsworks_75486; https://doi.org/10.1093/hmg/ddab023 |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.65C5C4DF |
| Database: |
BASE |