Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.
Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.
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DOI：
10.1111/ajt.14594
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3
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文献类型：
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作者：
Hernandez-Fuentes MP;Franklin C;Rebollo-Mesa I;Mollon J;Delaney F;Perucha E;Stapleton C;Borrows R;Byrne C;Cavalleri G;Clarke B;Clatworthy M;Feehally J;Fuggle S;Gagliano SA;Griffin S;Hammad A;Higgins R;Jardine A;Keogan M;Leach T;MacPhee I;Mark PB;Marsh J;Maxwell P;McKane W;McLean A;Newstead C;Augustine T;Phelan P;Powis S;Rowe P;Sheerin N;Solomon E;Stephens H;Thuraisingham R;Trembath R;Topham P;Vaughan R;Sacks SH;Conlon P;Opelz G;Soranzo N;Weale ME;Lord GM;United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3
免疫抑制的改善改变了已故供体同种异体移植物的短期存活率，但没有改变其长期失败率。供体和受体 HLA 之间的不匹配在针对移植物的急性和慢性同种异体免疫反应中发挥着重要作用。临床相关 HLA 基因座的完美匹配并不能消除免疫抑制的需要，这表明额外的遗传变异在短期和长期移植结果中发挥着关键作用。通过结合来自英国和欧盟的超国家队列的患者数据和样本，我们进行了第一个大规模全基因组关联研究，分析了 2094 个完整肾移植对中的供体和受体 DNA，并在 5866 个完整肾移植对中进行复制。我们研究了根据优先 HLA 匹配分配的死者供体移植物，这为 HLA 遗传效应提供了一些控制。在 HLA 区域之外，没有发现对长期或短期同种异体移植物存活有明显影响的供体或受体遗传效应。我们讨论对未来研究和临床应用的影响。迄今为止关于短期和长期肾移植结果的最大多中心全基因组关联研究没有发现 HLA 区域之外的基因座，凸显了表型异质性和样本量方面的挑战，同时也为未来的荟萃分析提供了参考数据集。
Improvements in immunosuppression have modified short‐term survival of deceased‐donor allografts, but not their rate of long‐term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short‐ and long‐term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large‐scale genome‐wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant‐pairs with replication in 5866 complete pairs. We studied deceased‐donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long‐ or short‐term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application. The largest multicenter genome‐wide association study to date on short‐ and long‐term renal transplantation outcomes finds no loci outside the HLA region, highlighting challenges in phenotypic heterogeneity and sample size while also providing a reference dataset for future meta‐analyses.
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DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
DOI：
10.1001/jama.1956.02960390027008
发表时间：
1956-01-01
影响因子：
120.7
作者：
MERRILL, JP;MURRAY, JE;GUILD, WR
通讯作者：
GUILD, WR
影响因子：
3.5
作者：
Mushiroda, T;Saito, S;Ohnishi, Y
通讯作者：
Ohnishi, Y
影响因子：
6.2
作者：
Nabokow, Alexander;Dobronravov, Vladimir A.;Kliem, Volker
通讯作者：
Kliem, Volker