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.; 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.; Pourcain, B.S.; Timpson, N.J.; Trollor, J.; 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.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, TIA; 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

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

Details

Download: 33517400_BIB_DFC20881CC51.pdf (1311.79 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_DFC20881CC51

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Human molecular genetics

Author(s)

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., 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., Pourcain B.S., Timpson N.J., Trollor J., 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.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 TIA, 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.

Working group(s)

CHARGE Inflammation Working Group

ISSN

1460-2083 (Electronic)

ISSN-L

0964-6906

Publication state

Published

Issued date

27/04/2021

Peer-reviewed

Oui

Volume

Number

Pages

393-409

Language

english

Notes

Publication types: Journal Article
Publication Status: ppublish

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.

URN

urn:nbn:ch:serval-BIB_DFC20881CC510

OAI-PMH

oai:serval.unil.ch:BIB_DFC20881CC51

DOI

10.1093/hmg/ddab023

Pubmed

33517400

Web of science

000654638100007

Open Access

Yes