Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy.
Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy.
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DOI：
10.2337/db11-0751
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发表时间：
2012-08
期刊：
影响因子：
7.7
通讯作者：
GENIE Consortium
中科院分区：
文献类型：
--
作者：
Williams WW;Salem RM;McKnight AJ;Sandholm N;Forsblom C;Taylor A;Guiducci C;McAteer JB;McKay GJ;Isakova T;Brennan EP;Sadlier DM;Palmer C;Söderlund J;Fagerholm E;Harjutsalo V;Lithovius R;Gordin D;Hietala K;Kytö J;Parkkonen M;Rosengård-Bärlund M;Thorn L;Syreeni A;Tolonen N;Saraheimo M;Wadén J;Pitkäniemi J;Sarti C;Tuomilehto J;Tryggvason K;Österholm AM;He B;Bain S;Martin F;Godson C;Hirschhorn JN;Maxwell AP;Groop PH;Florez JC;GENIE Consortium
我们成立了肾病遗传学--一个国际努力（GENIE）联盟，以研究先前报道的与1型糖尿病肾病（DN）相关的遗传学。GENIE由6，366名同样确定的欧洲血统的1型糖尿病参与者组成，有和没有DN，来自All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK。和爱尔兰共和国（英国- R.O.I.）收集和芬兰糖尿病肾病研究（FinnDiane），结合美国糖尿病肾脏遗传学研究（U.S. GoKinD）的重新分析数据。在英国，我们几乎没有发现EPO启动子多态性rs 161740与增殖性视网膜病变和终末期肾病联合表型相关的证据。R.O. I (odds比值[OR] 1.14，P = 0.19）或FinnDiane（OR 1.06，P = 0.60）。然而，一项包括先前报道的队列的固定效应荟萃分析保留了与该表型的全基因组显著相关性（OR 1.31，P = 2 × 10−9）。在美国，对ELMO 1基因座和据报道与DN相关的遗传区域进行了扩展调查，GoKinD仅对这些基因座产生了名义上的统计学显著性。最后，在最近的荟萃分析中确定的最佳候选人未能达到全基因组的意义。总之，我们无法复制大多数以前报道的DN的遗传关联，并且EPO启动子关联的重要性减弱。
We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated.
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DOI：
10.1073/pnas.0800454105
发表时间：
2008-05-13
影响因子：
11.1
作者：
Tong, Zongzhong;Yang, Zhenglin;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
8.2
作者：
NELSON, RG;NEWMAN, JM;BENNETT, PH
通讯作者：
BENNETT, PH
影响因子：
19.6
作者：
Lemley, KV
通讯作者：
Lemley, KV
影响因子：
1.9
作者：
Leak TS;Perlegas PS;Smith SG;Keene KL;Hicks PJ;Langefeld CD;Mychaleckyj JC;Rich SS;Kirk JK;Freedman BI;Bowden DW;Sale MM
通讯作者：
Sale MM
影响因子：
7.7
作者：
Shimazaki, A;Kawamura, Y;Maeda, S
通讯作者：
Maeda, S