Nidogen-1 could play a role in diabetic kidney disease development in type 2 diabetes: a genome-wide association meta-analysis.
Nidogen-1 could play a role in diabetic kidney disease development in type 2 diabetes: a genome-wide association meta-analysis.
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DOI：
10.1186/s40246-022-00422-y
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发表时间：
2022-10-21
期刊：
影响因子：
4.5
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中科院分区：
文献类型：
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糖尿病肾病（DKD）影响约40%的糖尿病患者。它是无法治愈的，通常会导致终末期肾病（ESRD）。DKD的发病机制尚未完全清楚，DKD的遗传学尚未得到广泛研究。在这项研究中，我们调查了2型糖尿病（T2 D）DKD的遗传基础，以提供更多的见解，疾病的发病机制。使用英国生物银行（UKBB）提供的数据，我们在13，123名T2 D患者中进行了DKD全基因组关联研究（GWAS）以及两项肌酐估计肾小球滤过率（eGFR）GWA研究：一项在26，786名T2 D患者中进行，另一项在339，080名非糖尿病患者中进行。我们还进行了一项DKD GWAS荟萃分析，将我们的结果与Innovative diabetes Tools（SUMMIT）联盟的微血管和大血管硬终点替代标记物发表的结果相结合。我们确认了先前报道的与慢性肾脏病（CKD）和T2 D患者eGFR相关的两个位点。UMOD-PDILT基因座与DKD（P = 1.17E−09）以及T2 D（P = 1.31E−15）和非糖尿病患者（P = 3.95E−73）的肌酐eGFR相关。PRKAG 2基因座与T2 D患者（P = 2.78E−10）和非T2 D患者（P = 5.65E−72）的肌酐eGFR相关。我们的荟萃分析揭示了DKD与nidogen-1（NID 1）基因的剪接数量性状位点（sQTL）rs72763500（chr 1：236116561）之间的新关联。我们的数据证实了先前报道的与T2 D中的CKD和肌酐eGFR相关的两个位点。它还表明，NID 1，肾小管基底膜的主要成分，可能在T2 D的DKD发展中发挥作用。虽然我们的NID 1发现仍有待复制，但它是更全面了解DKD发病机制的一步。在线版本包含补充材料，可通过10.1186/s40246-022-00422-y获得。
Diabetic kidney disease (DKD) affects about 40% of patients with diabetes. It is incurable and usually leads to end-stage renal disease (ESRD). The pathogenesis of DKD is still not fully understood, and the genetics of DKD have not yet been extensively studied. In this study, we investigate the genetic basis of DKD in type 2 diabetes (T2D) to provide more insights into the pathogenesis of the disease. Using the data provided by the UK Biobank (UKBB), we performed a DKD genome-wide association study (GWAS) in 13,123 individuals with T2D as well as two creatinine estimated glomerular filtration rate (eGFR) GWA studies: one in 26,786 individuals with T2D and the other in 339,080 non-diabetic individuals. We also conducted a DKD GWAS meta-analysis combining our results with those published by the surrogate markers for micro- and macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) consortium. We confirm two loci previously reported to be associated with chronic kidney disease (CKD) and eGFR in T2D. The UMOD-PDILT locus is associated with DKD (P = 1.17E−09) as well as creatinine eGFR in both people with T2D (P = 1.31E−15) and people without diabetes (P = 3.95E−73). The PRKAG2 locus is associated with creatinine eGFR in people with (P = 2.78E−10) and without (P = 5.65E−72) T2D. Our meta-analysis reveals a novel association between DKD and variant rs72763500 (chr1:236116561) which is a splicing quantitative trait locus (sQTL) for nidogen-1 (NID1) gene. Our data confirm two loci previously reported in association with CKD and creatinine eGFR in T2D. It also suggests that NID1, a major component of the renal tubular basement membrane, could play a role in DKD development in T2D. While our NID1 finding remains to be replicated, it is a step toward a more comprehensive understanding of DKD pathogenesis. The online version contains supplementary material available at 10.1186/s40246-022-00422-y.
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DOI：
10.1093/bioinformatics/bty185
发表时间：
2018-08-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Privé F;Aschard H;Ziyatdinov A;Blum MGB
通讯作者：
Blum MGB
影响因子：
3.7
作者：
Miner, Jeffrey H.
通讯作者：
Miner, Jeffrey H.
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
7.7
作者：
Shimazaki, A;Kawamura, Y;Maeda, S
通讯作者：
Maeda, S
影响因子：
16.6
作者：
Pattaro C;Teumer A;Gorski M;Chu AY;Li M;Mijatovic V;Garnaas M;Tin A;Sorice R;Li Y;Taliun D;Olden M;Foster M;Yang Q;Chen MH;Pers TH;Johnson AD;Ko YA;Fuchsberger C;Tayo B;Nalls M;Feitosa MF;Isaacs A;Dehghan A;d'Adamo P;Adeyemo A;Dieffenbach AK;Zonderman AB;Nolte IM;van der Most PJ;Wright AF;Shuldiner AR;Morrison AC;Hofman A;Smith AV;Dreisbach AW;Franke A;Uitterlinden AG;Metspalu A;Tonjes A;Lupo A;Robino A;Johansson Å;Demirkan A;Kollerits B;Freedman BI;Ponte B;Oostra BA;Paulweber B;Krämer BK;Mitchell BD;Buckley BM;Peralta CA;Hayward C;Helmer C;Rotimi CN;Shaffer CM;Müller C;Sala C;van Duijn CM;Saint-Pierre A;Ackermann D;Shriner D;Ruggiero D;Toniolo D;Lu Y;Cusi D;Czamara D;Ellinghaus D;Siscovick DS;Ruderfer D;Gieger C;Grallert H;Rochtchina E;Atkinson EJ;Holliday EG;Boerwinkle E;Salvi E;Bottinger EP;Murgia F;Rivadeneira F;Ernst F;Kronenberg F;Hu FB;Navis GJ;Curhan GC;Ehret GB;Homuth G;Coassin S;Thun GA;Pistis G;Gambaro G;Malerba G;Montgomery GW;Eiriksdottir G;Jacobs G;Li G;Wichmann HE;Campbell H;Schmidt H;Wallaschofski H;Völzke H;Brenner H;Kroemer HK;Kramer H;Lin H;Leach IM;Ford I;Guessous I;Rudan I;Prokopenko I;Borecki I;Heid IM;Kolcic I;Persico I;Jukema JW;Wilson JF;Felix JF;Divers J;Lambert JC;Stafford JM;Gaspoz JM;Smith JA;Faul JD;Wang JJ;Ding J;Hirschhorn JN;Attia J;Whitfield JB;Chalmers J;Viikari J;Coresh J;Denny JC;Karjalainen J;Fernandes JK;Endlich K;Butterbach K;Keene KL;Lohman K;Portas L;Launer LJ;Lyytikäinen LP;Yengo L;Franke L;Ferrucci L;Rose LM;Kedenko L;Rao M;Struchalin M;Kleber ME;Cavalieri M;Haun M;Cornelis MC;Ciullo M;Pirastu M;de Andrade M;McEvoy MA;Woodward M;Adam M;Cocca M;Nauck M;Imboden M;Waldenberger M;Pruijm M;Metzger M;Stumvoll M;Evans MK;Sale MM;Kähönen M;Boban M;Bochud M;Rheinberger M;Verweij N;Bouatia-Naji N;Martin NG;Hastie N;Probst-Hensch N;Soranzo N;Devuyst O;Raitakari O;Gottesman O;Franco OH;Polasek O;Gasparini P;Munroe PB;Ridker PM;Mitchell P;Muntner P;Meisinger C;Smit JH;ICBP Consortium;AGEN Consortium;CARDIOGRAM;CHARGe-Heart Failure Group;ECHOGen Consortium;Kovacs P;Wild PS;Froguel P;Rettig R;Mägi R;Biffar R;Schmidt R;Middelberg RP;Carroll RJ;Penninx BW;Scott RJ;Katz R;Sedaghat S;Wild SH;Kardia SL;Ulivi S;Hwang SJ;Enroth S;Kloiber S;Trompet S;Stengel B;Hancock SJ;Turner ST;Rosas SE;Stracke S;Harris TB;Zeller T;Zemunik T;Lehtimäki T;Illig T;Aspelund T;Nikopensius T;Esko T;Tanaka T;Gyllensten U;Völker U;Emilsson V;Vitart V;Aalto V;Gudnason V;Chouraki V;Chen WM;Igl W;März W;Koenig W;Lieb W;Loos RJ;Liu Y;Snieder H;Pramstaller PP;Parsa A;O'Connell JR;Susztak K;Hamet P;Tremblay J;de Boer IH;Böger CA;Goessling W;Chasman DI;Köttgen A;Kao WH;Fox CS
通讯作者：
Fox CS