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

Ahluwalia, Tarunveer S.; Prins, Bram P.; Abdollahi, Mohammadreza; Armstrong, Nicola J.; Aslibekyan, Stella; Bain, Lisa; Jefferis, Barbara; Baumert, Jens; Beekman, Marian; Ben-Shlomo, Yoav; Bis, Joshua C.; Mitchell, Braxton D.; Geus, Eco de; Delgado, Graciela E.; Marek, Diana; Eriksson, Joel; Kajantie, Eero; Kanoni, Stavroula; Kemp, John P.; Lu, Chen; Marioni, Riccardo E.; McLachlan, Stela; Milaneschi, Yuri; Nolte, Ilja M.; Petrelis, Alexandros M.; Porcu, Eleonora; Sabater-Lleal, Maria; Naderi, Elnaz; Seppälä, Tina and Singhal; Spector, Tim; Stacey, David; Stathopoulou, Maria G.; Tanaka, Toshiko; Wannamethee, S. Goya; Whincup, Peter; Rotter, Jerome I.; Dehghan, Abbas; Boerwinkle, Eric; Psaty, Bruce M.; Snieder, Harold; Alizadeh, Behrooz Z. and Müller-Nurasyid, Martina (2021): Genome-wide association study of circulating interleukin 6 levels identifies novel loci. In: Human Molecular Genetics, Vol. 30, No. 5: pp. 393-409

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 × 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.

• Item Type: Journal article
• Faculties: Medicine > Institute for Medical Information Processing, Biometry and Epidemiology
• Subjects: 600 Technology > 610 Medicine and health
• Annotation: Vollständige Autor*innen-Liste s. Volltext
• Language: English