Longitudinal Epigenome-Wide Analysis of Kidney Transplant Recipients Pretransplant and Posttransplant.
Longitudinal Epigenome-Wide Analysis of Kidney Transplant Recipients Pretransplant and Posttransplant.
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DOI：
10.1016/j.ekir.2022.11.001
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发表时间：
2023-02
影响因子：
6
通讯作者：
McKnight, Amy Jayne
中科院分区：
文献类型：
--
作者：
Smyth, Laura J.;Kerr, Katie R.;Kilner, Jill;McGill, Aine E.;Maxwell, Alexander P.;McKnight, Amy Jayne
关键词：
肾移植仍然是终末期肾病（ESRD）治疗的金标准，与透析相比，患者结局有所改善。DNA甲基化的表观全基因组关联分析（EWAS）可以识别有助于个体不良移植结果风险的标志物，但在肾移植受者中仅进行了有限数量的EWAS。EWAS旨在研究移植后并发症最少的肾移植受者队列的甲基化谱，探索移植前和移植后样本的差异。我们使用Infinium MethylationEPIC微阵列（Illumina，San Diego，CA）比较了移植前和移植后（N = 154）来自相同肾移植受者外周血单核细胞的样本中差异甲基化胞嘧啶-磷酸-鸟嘌呤位点（dmCpG）。接受者从已故捐赠者那里接受肾脏，平均随访17年。在错误发现率（FDR）校正P ≤ 9 × 10−8时，排名靠前的5个dmCpG存在显著差异; cg 23597162位于JAZF 1内，cg 25187293位于BTNL 8内，cg 17944885位于ZNF 788 P和ZNF 625-ZNF 20之间，cg 14655917位于ASB 4和PDK 4之间，cg 09839120位于GIMAP 6和EIF 2AP 3之间。在普遍接受的EWAS临界显著性水平FDR校正P（PFDRadj）≤ 9 × 10−8时，确定了5个dmCpG，包括cg 23597162（JAZF 1内）和cg 17944885，它们与慢性肾脏疾病（CKD）有既往相关性。比较没有移植后并发症证据的个体（N = 105）表明，693，555个CpG（89.57%）在甲基化方面没有任何显著差异（PFDRadj ≥ 0.05），因此该研究为未来寻求识别移植后并发症标志物的表观遗传学研究建立了重要参考。
Kidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual’s risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant. We compared differentially methylated cytosine-phosphate-guanine sites (dmCpGs) in samples derived from peripheral blood mononuclear cells of the same kidney transplant recipients, collected both pretransplant and posttransplant (N = 154), using the Infinium MethylationEPIC microarray (Illumina, San Diego, CA). Recipients received kidneys from deceased donors and had a mean of 17 years of follow-up. Five top-ranked dmCpGs were significantly different at false discovery rate (FDR) adjusted P ≤ 9 × 10−8; cg23597162 within JAZF1, cg25187293 within BTNL8, cg17944885, located between ZNF788P and ZNF625-ZNF20, cg14655917 located between ASB4 and PDK4 and cg09839120 located between GIMAP6 and EIF2AP3. Five dmCpGs were identified at the generally accepted EWAS critical significance level of FDR adjusted P (PFDRadj) ≤ 9 × 10−8, including cg23597162 (within JAZF1) and cg17944885, which have prior associations with chronic kidney disease (CKD). Comparing individuals with no evidence of posttransplant complications (N = 105) demonstrated that 693,555 CpGs (89.57%) did not display any significant difference in methylation (PFDRadj ≥ 0.05), thereby this study establishes an important reference for future epigenetic studies that seek to identify markers of posttransplant complications.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
16.6
作者：
Chu AY;Tin A;Schlosser P;Ko YA;Qiu C;Yao C;Joehanes R;Grams ME;Liang L;Gluck CA;Liu C;Coresh J;Hwang SJ;Levy D;Boerwinkle E;Pankow JS;Yang Q;Fornage M;Fox CS;Susztak K;Köttgen A
通讯作者：
Köttgen A
影响因子：
12.3
作者：
Breeze CE;Batorsky A;Lee MK;Szeto MD;Xu X;McCartney DL;Jiang R;Patki A;Kramer HJ;Eales JM;Raffield L;Lange L;Lange E;Durda P;Liu Y;Tracy RP;Van Den Berg D;NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed MESA Multi-Omics Working Group;Evans KL;Kraus WE;Shah S;Tiwari HK;Hou L;Whitsel EA;Jiang X;Charchar FJ;Baccarelli AA;Rich SS;Morris AP;Irvin MR;Arnett DK;Hauser ER;Rotter JI;Correa A;Hayward C;Horvath S;Marioni RE;Tomaszewski M;Beck S;Berndt SI;London SJ;Mychaleckyj JC;Franceschini N
通讯作者：
Franceschini N
影响因子：
64.5
作者：
Barros, Rafael Di Marco;Roberts, Natalie A.;Dart, Robin J.;Vantourout, Pierre;Jandke, Anett;Nussbaumer, Oliver;Deban, Livija;Cipolat, Sara;Hart, Rosie;Iannitto, Maria Luisa;Laing, Adam;Spencer-Dene, Bradley;East, Philip;Gibbons, Deena;Irving, Peter M.;Pereira, Pablo;Steinhoff, Ulrich;Hayday, Adrian
通讯作者：
Hayday, Adrian
影响因子：
4.5
作者：
Dayeh T;Volkov P;Salö S;Hall E;Nilsson E;Olsson AH;Kirkpatrick CL;Wollheim CB;Eliasson L;Rönn T;Bacos K;Ling C
通讯作者：
Ling C