A genome-wide association study identifies a novel major locus for glycemic control in type 1 diabetes, as measured by both A1C and glucose.
A genome-wide association study identifies a novel major locus for glycemic control in type 1 diabetes, as measured by both A1C and glucose.
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DOI：
10.2337/db09-0653
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发表时间：
2010-02
期刊：
影响因子：
7.7
通讯作者：
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
中科院分区：
文献类型：
--
作者：
Paterson AD;Waggott D;Boright AP;Hosseini SM;Shen E;Sylvestre MP;Wong I;Bharaj B;Cleary PA;Lachin JM;MAGIC (Meta-Analyses of Glucose and Insulin-related traits Consortium);Below JE;Nicolae D;Cox NJ;Canty AJ;Sun L;Bull SB;Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
血糖是1型糖尿病发生长期并发症的主要危险因素；然而，目前还没有发现1型糖尿病患者控制血糖的特定基因位点。为了在1型糖尿病中确定这样的基因位点，我们分析了糖尿病控制和并发症试验中A1C的纵向重复测量。我们在DCCT常规治疗组（n = 667）和强化治疗组（n = 637）中分别使用超过6.5年的季度A1C平均值进行了全基因组关联研究。在感兴趣的位点，使用线性混合模型来利用所有重复测量。然后我们评估了这些基因座与毛细血管血糖的关系，并重复测量了糖尿病的多种并发症。在常规治疗组中，我们在SORCS1附近发现了A1C水平的一个主要位点（10q25.1, P = 7 × 10−10），它也与平均血糖有关（P = 2 × 10−5）。强化治疗组的糖化血红蛋白证实了这一点（P = 0.01）。其他基因座获得了接近全基因组意义的证据：联合治疗组的14q32.13 （GSC）和9p22 (BNC2)，强化组的15q21.3 （WDR72）。此外，这些基因座提供了与糖尿病并发症相关的证据，特别是SORCS1与低血糖有关，BNC2与肾脏和视网膜并发症有关。我们重复了SORCS1与肾脏糖尿病遗传学（GoKinD）研究对照受试者的关联（P = 0.01）以及BNC2与非糖尿病个体A1C的关联。糖尿病患者糖化血红蛋白和葡萄糖的主要位点在SORCS1附近。这可能会影响试图确定长期糖尿病并发症危险因素的遗传研究的设计和分析。
Glycemia is a major risk factor for the development of long-term complications in type 1 diabetes; however, no specific genetic loci have been identified for glycemic control in individuals with type 1 diabetes. To identify such loci in type 1 diabetes, we analyzed longitudinal repeated measures of A1C from the Diabetes Control and Complications Trial. We performed a genome-wide association study using the mean of quarterly A1C values measured over 6.5 years, separately in the conventional (n = 667) and intensive (n = 637) treatment groups of the DCCT. At loci of interest, linear mixed models were used to take advantage of all the repeated measures. We then assessed the association of these loci with capillary glucose and repeated measures of multiple complications of diabetes. We identified a major locus for A1C levels in the conventional treatment group near SORCS1 (10q25.1, P = 7 × 10−10), which was also associated with mean glucose (P = 2 × 10−5). This was confirmed using A1C in the intensive treatment group (P = 0.01). Other loci achieved evidence close to genome-wide significance: 14q32.13 (GSC) and 9p22 (BNC2) in the combined treatment groups and 15q21.3 (WDR72) in the intensive group. Further, these loci gave evidence for association with diabetic complications, specifically SORCS1 with hypoglycemia and BNC2 with renal and retinal complications. We replicated the SORCS1 association in Genetics of Diabetes in Kidneys (GoKinD) study control subjects (P = 0.01) and the BNC2 association with A1C in nondiabetic individuals. A major locus for A1C and glucose in individuals with diabetes is near SORCS1. This may influence the design and analysis of genetic studies attempting to identify risk factors for long-term diabetic complications.
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影响因子：
7.7
作者：
Bonnefond A;Vaxillaire M;Labrune Y;Lecoeur C;Chèvre JC;Bouatia-Naji N;Cauchi S;Balkau B;Marre M;Tichet J;Riveline JP;Hadjadj S;Gallois Y;Czernichow S;Hercberg S;Kaakinen M;Wiesner S;Charpentier G;Lévy-Marchal C;Elliott P;Jarvelin MR;Horber F;Dina C;Pedersen O;Sladek R;Meyre D;Froguel P
通讯作者：
Froguel P
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
7.7
作者：
Cleary, Patricia A.;Orchard, Trevor J.;Nathan, David M.
通讯作者：
Nathan, David M.
影响因子：
64.8
作者：
Chanock, Stephen J.;Manolio, Teri;Collins, Francis S.
通讯作者：
Collins, Francis S.
影响因子：
3.6
作者：
Gerstl, E. -M.;Rabl, W.;Holl, R. W.
通讯作者：
Holl, R. W.