Epigenome-wide association studies identify DNA methylation associated with kidney function.
Epigenome-wide association studies identify DNA methylation associated with kidney function.
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DOI：
10.1038/s41467-017-01297-7
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发表时间：
2017-11-03
影响因子：
16.6
通讯作者：
Köttgen A
中科院分区：
文献类型：
--
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
慢性肾病（CKD）的定义是肾小球滤过率（eGFR）估计值降低。以前的遗传学研究已经涉及到导致CKD的调节机制。在这里，我们使用2264名ARIC研究和2595名Frachial Heart研究参与者的全血DNA甲基化来识别肾功能的表观遗传特征，提出了eGFR和CKD的表观基因组关联研究。在19个与eGFR/CKD显著相关（P <1 e-07）并重复的CpG位点中，5个也与CKD患者活检中的肾纤维化相关，并在肾皮质中显示一致的DNA甲基化变化。PTPN 6/PHB 2、ANKRD 11和TNRC 18处的前导CpG映射到肾皮质中的活性增强子。在PTPN 6/PHB 2 cg 19942083中，肾皮质甲基化与较低的肾PTPN 6表达、较高的eGFR和较少的肾纤维化相关。含有243个eGFR相关（P <1 e-05）CpG的区域显著富集EBF 1、EP 300和CEBPB的转录因子结合位点（P < 5e-6）。我们的发现强调了肾功能相关的表观遗传变异。肾功能的全基因组关联研究显示，在调控区相关遗传变异富集。在这里，作者进行了肾功能和疾病的表观基因组关联研究，确定了19个与这些显著相关的CpG位点。
Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs at PTPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex. At PTPN6/PHB2 cg19942083, methylation in kidney cortex associates with lower renal PTPN6 expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation. Genome-wide association studies of kidney function show enrichment of associated genetic variants in regulatory regions. Here, the authors perform epigenome-wide association studies of kidney function and disease, identifying 19 CpG sites significantly associated with these.
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影响因子：
30.8
作者：
Liu C;Kraja AT;Smith JA;Brody JA;Franceschini N;Bis JC;Rice K;Morrison AC;Lu Y;Weiss S;Guo X;Palmas W;Martin LW;Chen YD;Surendran P;Drenos F;Cook JP;Auer PL;Chu AY;Giri A;Zhao W;Jakobsdottir J;Lin LA;Stafford JM;Amin N;Mei H;Yao J;Voorman A;CHD Exome+ Consortium;ExomeBP Consortium;GoT2DGenes Consortium;T2D-GENES Consortium;Larson MG;Grove ML;Smith AV;Hwang SJ;Chen H;Huan T;Kosova G;Stitziel NO;Kathiresan S;Samani N;Schunkert H;Deloukas P;Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia;Li M;Fuchsberger C;Pattaro C;Gorski M;CKDGen Consortium;Kooperberg C;Papanicolaou GJ;Rossouw JE;Faul JD;Kardia SL;Bouchard C;Raffel LJ;Uitterlinden AG;Franco OH;Vasan RS;O'Donnell CJ;Taylor KD;Liu K;Bottinger EP;Gottesman O;Daw EW;Giulianini F;Ganesh S;Salfati E;Harris TB;Launer LJ;Dörr M;Felix SB;Rettig R;Völzke H;Kim E;Lee WJ;Lee IT;Sheu WH;Tsosie KS;Edwards DR;Liu Y;Correa A;Weir DR;Völker U;Ridker PM;Boerwinkle E;Gudnason V;Reiner AP;van Duijn CM;Borecki IB;Edwards TL;Chakravarti A;Rotter JI;Psaty BM;Loos RJ;Fornage M;Ehret GB;Newton-Cheh C;Levy D;Chasman DI
通讯作者：
Chasman DI
影响因子：
3
作者：
Martin TC;Yet I;Tsai PC;Bell JT
通讯作者：
Bell JT
影响因子：
168.9
作者：
Matsushita, Kunihiro;van der Velde, Marije;Astor, Brad C.;Woodward, Mark;Levey, Andrew S.;de Jong, Paul E.;Coresh, Josef;Gansevoort, Ron T.
通讯作者：
Gansevoort, Ron T.
影响因子：
12.3
作者：
Ligthart S;Marzi C;Aslibekyan S;Mendelson MM;Conneely KN;Tanaka T;Colicino E;Waite LL;Joehanes R;Guan W;Brody JA;Elks C;Marioni R;Jhun MA;Agha G;Bressler J;Ward-Caviness CK;Chen BH;Huan T;Bakulski K;Salfati EL;WHI-EMPC Investigators;Fiorito G;CHARGE epigenetics of Coronary Heart Disease;Wahl S;Schramm K;Sha J;Hernandez DG;Just AC;Smith JA;Sotoodehnia N;Pilling LC;Pankow JS;Tsao PS;Liu C;Zhao W;Guarrera S;Michopoulos VJ;Smith AK;Peters MJ;Melzer D;Vokonas P;Fornage M;Prokisch H;Bis JC;Chu AY;Herder C;Grallert H;Yao C;Shah S;McRae AF;Lin H;Horvath S;Fallin D;Hofman A;Wareham NJ;Wiggins KL;Feinberg AP;Starr JM;Visscher PM;Murabito JM;Kardia SL;Absher DM;Binder EB;Singleton AB;Bandinelli S;Peters A;Waldenberger M;Matullo G;Schwartz JD;Demerath EW;Uitterlinden AG;van Meurs JB;Franco OH;Chen YI;Levy D;Turner ST;Deary IJ;Ressler KJ;Dupuis J;Ferrucci L;Ong KK;Assimes TL;Boerwinkle E;Koenig W;Arnett DK;Baccarelli AA;Benjamin EJ;Dehghan A
通讯作者：
Dehghan A
影响因子：
8.8
作者：
Breeze CE;Paul DS;van Dongen J;Butcher LM;Ambrose JC;Barrett JE;Lowe R;Rakyan VK;Iotchkova V;Frontini M;Downes K;Ouwehand WH;Laperle J;Jacques PÉ;Bourque G;Bergmann AK;Siebert R;Vellenga E;Saeed S;Matarese F;Martens JHA;Stunnenberg HG;Teschendorff AE;Herrero J;Birney E;Dunham I;Beck S
通讯作者：
Beck S