Genome-wide association study of circulating interleukin 6 levels identifies novel loci.
Genome-wide association study of circulating interleukin 6 levels identifies novel loci.
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循环白细胞介素6水平的全基因组关联研究确定了新的位点
DOI：
10.1093/hmg/ddab023
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发表时间：
2021-04-27
影响因子：
3.5
通讯作者：
Alizadeh BZ
中科院分区：
文献类型：
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作者：
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;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 YC;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
白细胞介素6（IL-6）是一种多功能细胞因子，具有促炎和抗炎特性，遗传率估计高达61%。血液中IL-6的循环水平与复杂疾病发病机制的风险增加有关。我们进行了一项两阶段的发现和复制全基因组关联研究（GWAS），包括多达67 428（ndiscovery = 52 654和nreplication = 14 774）个欧洲血统的个体的循环血清IL-6水平。在所有样本的联合荟萃分析中，基于发现荟萃分析的逆方差固定效应，然后重复，鉴定出两个独立的基因座，染色体（Chr）2q14上的IL1F10/IL1RN rs6734238（P组合= 1.8 × 10 − 11），Chr 6p21上的HLA-DRB 1/DRB 5 rs660895（P组合= 1.5 × 10 − 10）。我们还复制了Chr1q21上的IL6R rs4537545位点（P组合= 1.2 × 10 − 122）。我们的研究确定了循环IL-6水平的新位点，揭示了可能影响IL-6病理生物学的新的免疫和炎症途径。
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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影响因子：
37.8
作者：
Dehghan A;Dupuis J;Barbalic M;Bis JC;Eiriksdottir G;Lu C;Pellikka N;Wallaschofski H;Kettunen J;Henneman P;Baumert J;Strachan DP;Fuchsberger C;Vitart V;Wilson JF;Paré G;Naitza S;Rudock ME;Surakka I;de Geus EJ;Alizadeh BZ;Guralnik J;Shuldiner A;Tanaka T;Zee RY;Schnabel RB;Nambi V;Kavousi M;Ripatti S;Nauck M;Smith NL;Smith AV;Sundvall J;Scheet P;Liu Y;Ruokonen A;Rose LM;Larson MG;Hoogeveen RC;Freimer NB;Teumer A;Tracy RP;Launer LJ;Buring JE;Yamamoto JF;Folsom AR;Sijbrands EJ;Pankow J;Elliott P;Keaney JF;Sun W;Sarin AP;Fontes JD;Badola S;Astor BC;Hofman A;Pouta A;Werdan K;Greiser KH;Kuss O;Meyer zu Schwabedissen HE;Thiery J;Jamshidi Y;Nolte IM;Soranzo N;Spector TD;Völzke H;Parker AN;Aspelund T;Bates D;Young L;Tsui K;Siscovick DS;Guo X;Rotter JI;Uda M;Schlessinger D;Rudan I;Hicks AA;Penninx BW;Thorand B;Gieger C;Coresh J;Willemsen G;Harris TB;Uitterlinden AG;Järvelin MR;Rice K;Radke D;Salomaa V;Willems van Dijk K;Boerwinkle E;Vasan RS;Ferrucci L;Gibson QD;Bandinelli S;Snieder H;Boomsma DI;Xiao X;Campbell H;Hayward C;Pramstaller PP;van Duijn CM;Peltonen L;Psaty BM;Gudnason V;Ridker PM;Homuth G;Koenig W;Ballantyne CM;Witteman JC;Benjamin EJ;Perola M;Chasman DI
通讯作者：
Chasman DI
影响因子：
3.7
作者：
Comuzzie AG;Cole SA;Laston SL;Voruganti VS;Haack K;Gibbs RA;Butte NF
通讯作者：
Butte NF
DOI：
10.1016/j.jaci.2012.03.018
发表时间：
2012-08
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Hawkins GA;Robinson MB;Hastie AT;Li X;Li H;Moore WC;Howard TD;Busse WW;Erzurum SC;Wenzel SE;Peters SP;Meyers DA;Bleecker ER;National Heart, Lung, and Blood Institute–sponsored Severe Asthma Research Program (SARP)
通讯作者：
National Heart, Lung, and Blood Institute–sponsored Severe Asthma Research Program (SARP)
影响因子：
3.7
作者：
Pei YF;Zhang L;Li J;Deng HW
通讯作者：
Deng HW
影响因子：
39.3
作者：
Harrison SC;Smith AJ;Jones GT;Swerdlow DI;Rampuri R;Bown MJ;Aneurysm Consortium;Folkersen L;Baas AF;de Borst GJ;Blankensteijn JD;Price JF;van der Graaf Y;McLachlan S;Agu O;Hofman A;Uitterlinden AG;Franco-Cereceda A;Ruigrok YM;van't Hof FN;Powell JT;van Rij AM;Casas JP;Eriksson P;Holmes MV;Asselbergs FW;Hingorani AD;Humphries SE
通讯作者：
Humphries SE