Genome-wide association study of circulating interleukin 6 levels identifies novel loci.
Tarunveer Singh AhluwaliaBram P PrinsMohammadreza AbdollahiNicola J ArmstrongStella AslibekyanLisa BainBarbara JefferisJens BaumertMarian BeekmanYoav Ben-ShlomoJoshua C BisBraxton D MitchellEco de GeusGraciela E DelgadoDiana MarekJoel ErikssonEero KajantieStavroula KanoniJohn P KempChen LuRiccardo E MarioniStela McLachlanYuri MilaneschiIlja M NolteAlexandros M PetrelisEleonora PorcuMaria Sabater-LlealElnaz NaderiIlkka SeppäläTina ShahGaurav SinghalMarie StandlAlexander TeumerAnbupalam ThalamuthuElisabeth ThieringStella TrompetChristie M BallantyneEmelia J BenjaminJuan P CasasCatherine TobenGeorge DedoussisJoris DeelenPeter DurdaJorgen EngmannMary F FeitosaHarald GrallertAnn HammarstedtSarah E HarrisGeorg HomuthJouke-Jan HottengaSirpa JalkanenYalda JamshidiMagdalene C JawaharTine JessMika KivimakiMarcus E KleberJari LahtiYongmei LiuPedro Marques-VidalDan MellströmSimon P MooijaartMartina Müller-NuraysidBrenda PenninxJoana A RevezPeter RossingKatri RäikkönenNaveed SattarHubert ScharnaglBengt SennbladAngela SilveiraBeate St PourcainNicholas J TimpsonJulian Trollornull nullJenny van DongenDiana Van HeemstSophie Visvikis-SiestPeter VollenweiderUwe VölkerMelanie WaldenbergerGonneke WillemsenDelilah ZabanehRichard W MorrisDonna K ArnettBernhard T BauneDorret I BoomsmaYen-Pei C ChangIan J DearyPanos DeloukasJohan G ErikssonDavid M EvansManuel A FerreiraTom GauntVilmundur GudnasonAnders HamstenJoachim HeinrichAroon HingoraniSteve E HumphriesJ Wouter JukemaWolfgang KoenigMeena KumariZoltan KutalikDeborah A LawlorTerho LehtimäkiWinfried MärzKaren A MatherSilvia NaitzaMatthias NauckClaes OhlssonJackie F PriceOlli RaitakariKen RicePerminder S SachdevEline SlagboomThorkild I A SørensenTim SpectorDavid StaceyMaria G StathopoulouToshiko TanakaS Goya WannametheePeter WhincupJerome I RotterAbbas DehghanEric BoerwinkleBruce M PsatyHarold SniederBehrooz Z AlizadehPublished in: Human molecular genetics (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.