Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.
Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.
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DOI：
10.2337/db16-0470
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发表时间：
2016-12
期刊：
影响因子：
7.7
通讯作者：
Kolaczyk ED
中科院分区：
文献类型：
--
作者：
Chen BH;Hivert MF;Peters MJ;Pilling LC;Hogan JD;Pham LM;Harries LW;Fox CS;Bandinelli S;Dehghan A;Hernandez DG;Hofman A;Hong J;Joehanes R;Johnson AD;Munson PJ;Rybin DV;Singleton AB;Uitterlinden AG;Ying S;MAGIC Investigators;Melzer D;Levy D;van Meurs JB;Ferrucci L;Florez JC;Dupuis J;Meigs JB;Kolaczyk ED
全基因组关联研究（GWAS）已经成功地确定了与血糖性状相关的遗传位点。然而，表征这些基因座的功能意义已被证明具有挑战性。我们试图通过使用基因表达微阵列数据来深入了解空腹胰岛素和空腹血糖的调节，这些数据来自FHS（n = 5，056）、鹿特丹研究（n = 723）和InCHIANTI研究（Invecchiare in Chianti）（n = 595）中无糖尿病参与者的外周血样本。使用错误发现率q <0.05，在调整年龄，性别，技术协变量和全血细胞计数后，我们确定了3个与空腹血糖相关的转录本和433个与空腹胰岛素水平相关的转录本。在这些发现中，在FHS和RS中，循环IGF 2BP 2转录水平与空腹胰岛素呈正相关。使用1000个基因组的基因型数据，我们确定了47,587个顺式表达数量性状位点（eQTL）和6,695个反式eQTL与433个显著的胰岛素相关转录本相关。值得注意的是，我们确定了一个trans-eQTL（rs 592423），其中A等位基因与较高的IGF 2BP 2水平和空腹胰岛素相关，这是一项由50，823名个体组成的独立遗传荟萃分析。我们的结论是，基因组和转录组数据的整合涉及循环IGF 2BP 2 mRNA水平与葡萄糖和胰岛素稳态。
Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes–imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis.
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影响因子：
30.8
作者：
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium;Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium;South Asian Type 2 Diabetes (SAT2D) Consortium;Mexican American Type 2 Diabetes (MAT2D) Consortium;Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium;Mahajan A;Go MJ;Zhang W;Below JE;Gaulton KJ;Ferreira T;Horikoshi M;Johnson AD;Ng MC;Prokopenko I;Saleheen D;Wang X;Zeggini E;Abecasis GR;Adair LS;Almgren P;Atalay M;Aung T;Baldassarre D;Balkau B;Bao Y;Barnett AH;Barroso I;Basit A;Been LF;Beilby J;Bell GI;Benediktsson R;Bergman RN;Boehm BO;Boerwinkle E;Bonnycastle LL;Burtt N;Cai Q;Campbell H;Carey J;Cauchi S;Caulfield M;Chan JC;Chang LC;Chang TJ;Chang YC;Charpentier G;Chen CH;Chen H;Chen YT;Chia KS;Chidambaram M;Chines PS;Cho NH;Cho YM;Chuang LM;Collins FS;Cornelis MC;Couper DJ;Crenshaw AT;van Dam RM;Danesh J;Das D;de Faire U;Dedoussis G;Deloukas P;Dimas AS;Dina C;Doney AS;Donnelly PJ;Dorkhan M;van Duijn C;Dupuis J;Edkins S;Elliott P;Emilsson V;Erbel R;Eriksson JG;Escobedo J;Esko T;Eury E;Florez JC;Fontanillas P;Forouhi NG;Forsen T;Fox C;Fraser RM;Frayling TM;Froguel P;Frossard P;Gao Y;Gertow K;Gieger C;Gigante B;Grallert H;Grant GB;Grrop LC;Groves CJ;Grundberg E;Guiducci C;Hamsten A;Han BG;Hara K;Hassanali N;Hattersley AT;Hayward C;Hedman AK;Herder C;Hofman A;Holmen OL;Hovingh K;Hreidarsson AB;Hu C;Hu FB;Hui J;Humphries SE;Hunt SE;Hunter DJ;Hveem K;Hydrie ZI;Ikegami H;Illig T;Ingelsson E;Islam M;Isomaa B;Jackson AU;Jafar T;James A;Jia W;Jöckel KH;Jonsson A;Jowett JB;Kadowaki T;Kang HM;Kanoni S;Kao WH;Kathiresan S;Kato N;Katulanda P;Keinanen-Kiukaanniemi KM;Kelly AM;Khan H;Khaw KT;Khor CC;Kim HL;Kim S;Kim YJ;Kinnunen L;Klopp N;Kong A;Korpi-Hyövälti E;Kowlessur S;Kraft P;Kravic J;Kristensen MM;Krithika S;Kumar A;Kumate J;Kuusisto J;Kwak SH;Laakso M;Lagou V;Lakka TA;Langenberg C;Langford C;Lawrence R;Leander K;Lee JM;Lee NR;Li M;Li X;Li Y;Liang J;Liju S;Lim WY;Lind L;Lindgren CM;Lindholm E;Liu CT;Liu JJ;Lobbens S;Long J;Loos RJ;Lu W;Luan J;Lyssenko V;Ma RC;Maeda S;Mägi R;Männisto S;Matthews DR;Meigs JB;Melander O;Metspalu A;Meyer J;Mirza G;Mihailov E;Moebus S;Mohan V;Mohlke KL;Morris AD;Mühleisen TW;Müller-Nurasyid M;Musk B;Nakamura J;Nakashima E;Navarro P;Ng PK;Nica AC;Nilsson PM;Njølstad I;Nöthen MM;Ohnaka K;Ong TH;Owen KR;Palmer CN;Pankow JS;Park KS;Parkin M;Pechlivanis S;Pedersen NL;Peltonen L;Perry JR;Peters A;Pinidiyapathirage JM;Platou CG;Potter S;Price JF;Qi L;Radha V;Rallidis L;Rasheed A;Rathman W;Rauramaa R;Raychaudhuri S;Rayner NW;Rees SD;Rehnberg E;Ripatti S;Robertson N;Roden M;Rossin EJ;Rudan I;Rybin D;Saaristo TE;Salomaa V;Saltevo J;Samuel M;Sanghera DK;Saramies J;Scott J;Scott LJ;Scott RA;Segrè AV;Sehmi J;Sennblad B;Shah N;Shah S;Shera AS;Shu XO;Shuldiner AR;Sigurđsson G;Sijbrands E;Silveira A;Sim X;Sivapalaratnam S;Small KS;So WY;Stančáková A;Stefansson K;Steinbach G;Steinthorsdottir V;Stirrups K;Strawbridge RJ;Stringham HM;Sun Q;Suo C;Syvänen AC;Takayanagi R;Takeuchi F;Tay WT;Teslovich TM;Thorand B;Thorleifsson G;Thorsteinsdottir U;Tikkanen E;Trakalo J;Tremoli E;Trip MD;Tsai FJ;Tuomi T;Tuomilehto J;Uitterlinden AG;Valladares-Salgado A;Vedantam S;Veglia F;Voight BF;Wang C;Wareham NJ;Wennauer R;Wickremasinghe AR;Wilsgaard T;Wilson JF;Wiltshire S;Winckler W;Wong TY;Wood AR;Wu JY;Wu Y;Yamamoto K;Yamauchi T;Yang M;Yengo L;Yokota M;Young R;Zabaneh D;Zhang F;Zhang R;Zheng W;Zimmet PZ;Altshuler D;Bowden DW;Cho YS;Cox NJ;Cruz M;Hanis CL;Kooner J;Lee JY;Seielstad M;Teo YY;Boehnke M;Parra EJ;Chambers JC;Tai ES;McCarthy MI;Morris AP
通讯作者：
Morris AP
影响因子：
30.8
作者：
Shin, So-Youn;Fauman, Eric B.;Petersen, Ann-Kristin;Krumsiek, Jan;Santos, Rita;Huang, Jie;Arnold, Matthias;Erte, Idil;Forgetta, Vincenzo;Yang, Tsun-Po;Walter, Klaudia;Menni, Cristina;Chen, Lu;Vasquez, Louella;Valdes, Ana M.;Hyde, Craig L.;Wang, Vicky;Ziemek, Daniel;Roberts, Phoebe;Xi, Li;Grundberg, Elin;Waldenberger, Melanie;Richards, J. Brent;Mohney, Robert P.;Milburn, Michael V.;John, Sally L.;Trimmer, Jeff;Theis, Fabian J.;Overington, John P.;Suhre, Karsten;Brosnan, M. Julia;Gieger, Christian;Kastenmueller, Gabi;Spector, Tim D.;Soranzo, Nicole
通讯作者：
Soranzo, Nicole
影响因子：
16.6
作者：
Peters MJ;Joehanes R;Pilling LC;Schurmann C;Conneely KN;Powell J;Reinmaa E;Sutphin GL;Zhernakova A;Schramm K;Wilson YA;Kobes S;Tukiainen T;NABEC/UKBEC Consortium;Ramos YF;Göring HH;Fornage M;Liu Y;Gharib SA;Stranger BE;De Jager PL;Aviv A;Levy D;Murabito JM;Munson PJ;Huan T;Hofman A;Uitterlinden AG;Rivadeneira F;van Rooij J;Stolk L;Broer L;Verbiest MM;Jhamai M;Arp P;Metspalu A;Tserel L;Milani L;Samani NJ;Peterson P;Kasela S;Codd V;Peters A;Ward-Caviness CK;Herder C;Waldenberger M;Roden M;Singmann P;Zeilinger S;Illig T;Homuth G;Grabe HJ;Völzke H;Steil L;Kocher T;Murray A;Melzer D;Yaghootkar H;Bandinelli S;Moses EK;Kent JW;Curran JE;Johnson MP;Williams-Blangero S;Westra HJ;McRae AF;Smith JA;Kardia SL;Hovatta I;Perola M;Ripatti S;Salomaa V;Henders AK;Martin NG;Smith AK;Mehta D;Binder EB;Nylocks KM;Kennedy EM;Klengel T;Ding J;Suchy-Dicey AM;Enquobahrie DA;Brody J;Rotter JI;Chen YD;Houwing-Duistermaat J;Kloppenburg M;Slagboom PE;Helmer Q;den Hollander W;Bean S;Raj T;Bakhshi N;Wang QP;Oyston LJ;Psaty BM;Tracy RP;Montgomery GW;Turner ST;Blangero J;Meulenbelt I;Ressler KJ;Yang J;Franke L;Kettunen J;Visscher PM;Neely GG;Korstanje R;Hanson RL;Prokisch H;Ferrucci L;Esko T;Teumer A;van Meurs JB;Johnson AD
通讯作者：
Johnson AD
影响因子：
7.7
作者：
Saxena R;Saleheen D;Been LF;Garavito ML;Braun T;Bjonnes A;Young R;Ho WK;Rasheed A;Frossard P;Sim X;Hassanali N;Radha V;Chidambaram M;Liju S;Rees SD;Ng DP;Wong TY;Yamauchi T;Hara K;Tanaka Y;Hirose H;McCarthy MI;Morris AP;DIAGRAM;MuTHER;AGEN;Basit A;Barnett AH;Katulanda P;Matthews D;Mohan V;Wander GS;Singh JR;Mehra NK;Ralhan S;Kamboh MI;Mulvihill JJ;Maegawa H;Tobe K;Maeda S;Cho YS;Tai ES;Kelly MA;Chambers JC;Kooner JS;Kadowaki T;Deloukas P;Rader DJ;Danesh J;Sanghera DK
通讯作者：
Sanghera DK
影响因子：
7.7
作者：
Burgess, Stephen;Thompson, Simon G.
通讯作者：
Thompson, Simon G.