Clonal myelopoiesis promotes adverse outcomes in chronic kidney disease.
Clonal myelopoiesis promotes adverse outcomes in chronic kidney disease.
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DOI：
10.1038/s41375-021-01382-3
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发表时间：
2022-03
期刊：
影响因子：
11.4
通讯作者：
Cross NCP
中科院分区：
文献类型：
--
作者：
Dawoud AAZ;Gilbert RD;Tapper WJ;Cross NCP
我们试图确定年龄相关的克隆性造血（CH）和慢性肾脏病（CKD）之间的关系。在5449例（2.9%）合格的英国生物样本库参与者（n = 190，487，中位年龄= 58岁）中确定了CH，定义为嵌合染色体异常（mCA）和/或驱动突变。CH与根据胱抑素-C估计的肾小球滤过率呈负相关（eGFR.cys; β =-0.75，P = 2.37 × 10-4），但与根据肌酐估计的eGFR无关，并且与根据eGFR.cys < 60定义的CKD特异性相关（OR = 1.02，P = 8.44 × 10-8）。在没有髓系肿瘤的参与者中，eGFR.cys与髓系mCA相关（n = 148，β =-3.36，P = 0.01）和体细胞驱动突变（n = 3241，β =-1.08，P = 6.25 × 10-5）与髓样肿瘤相关（髓样CH），特别是CBL、TET 2、JAK 2、PPM 1D和GNB 1中的突变，但不是DNMT 3A或ASXL 1。在无心血管疾病或髓系肿瘤病史的受试者中，与无髓系CH的受试者相比，髓系CH增加了CKD不良结局的风险（HR = 1.6，P = 0.002）。孟德尔随机化分析为CH和CKD之间的因果关系提供了提示性证据（P = 0.03）。我们得出结论，CH，特别是髓系CH，与eGFR. cys定义的CKD相关。髓样CH促进CKD的不良结局，强调内在和外在因素之间的相互作用对确定CH相关健康风险的重要性。
We sought to determine the relationship between age-related clonal hematopoiesis (CH) and chronic kidney disease (CKD). CH, defined as mosaic chromosome abnormalities (mCA) and/or driver mutations was identified in 5449 (2.9%) eligible UK Biobank participants (n = 190,487 median age = 58 years). CH was negatively associated with glomerular filtration rate estimated from cystatin-C (eGFR.cys; β = −0.75, P = 2.37 × 10–4), but not with eGFR estimated from creatinine, and was specifically associated with CKD defined by eGFR.cys < 60 (OR = 1.02, P = 8.44 × 10–8). In participants without prevalent myeloid neoplasms, eGFR.cys was associated with myeloid mCA (n = 148, β = −3.36, P = 0.01) and somatic driver mutations (n = 3241, β = −1.08, P = 6.25 × 10–5) associated with myeloid neoplasia (myeloid CH), specifically mutations in CBL, TET2, JAK2, PPM1D and GNB1 but not DNMT3A or ASXL1. In participants with no history of cardiovascular disease or myeloid neoplasms, myeloid CH increased the risk of adverse outcomes in CKD (HR = 1.6, P = 0.002) compared to those without myeloid CH. Mendelian randomisation analysis provided suggestive evidence for a causal relationship between CH and CKD (P = 0.03). We conclude that CH, and specifically myeloid CH, is associated with CKD defined by eGFR.cys. Myeloid CH promotes adverse outcomes in CKD, highlighting the importance of the interaction between intrinsic and extrinsic factors to define the health risk associated with CH.
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影响因子：
64.8
作者：
Bick AG;Weinstock JS;Nandakumar SK;Fulco CP;Bao EL;Zekavat SM;Szeto MD;Liao X;Leventhal MJ;Nasser J;Chang K;Laurie C;Burugula BB;Gibson CJ;Lin AE;Taub MA;Aguet F;Ardlie K;Mitchell BD;Barnes KC;Moscati A;Fornage M;Redline S;Psaty BM;Silverman EK;Weiss ST;Palmer ND;Vasan RS;Burchard EG;Kardia SLR;He J;Kaplan RC;Smith NL;Arnett DK;Schwartz DA;Correa A;de Andrade M;Guo X;Konkle BA;Custer B;Peralta JM;Gui H;Meyers DA;McGarvey ST;Chen IY;Shoemaker MB;Peyser PA;Broome JG;Gogarten SM;Wang FF;Wong Q;Montasser ME;Daya M;Kenny EE;North KE;Launer LJ;Cade BE;Bis JC;Cho MH;Lasky-Su J;Bowden DW;Cupples LA;Mak ACY;Becker LC;Smith JA;Kelly TN;Aslibekyan S;Heckbert SR;Tiwari HK;Yang IV;Heit JA;Lubitz SA;Johnsen JM;Curran JE;Wenzel SE;Weeks DE;Rao DC;Darbar D;Moon JY;Tracy RP;Buth EJ;Rafaels N;Loos RJF;Durda P;Liu Y;Hou L;Lee J;Kachroo P;Freedman BI;Levy D;Bielak LF;Hixson JE;Floyd JS;Whitsel EA;Ellinor PT;Irvin MR;Fingerlin TE;Raffield LM;Armasu SM;Wheeler MM;Sabino EC;Blangero J;Williams LK;Levy BD;Sheu WH;Roden DM;Boerwinkle E;Manson JE;Mathias RA;Desai P;Taylor KD;Johnson AD;NHLBI Trans-Omics for Precision Medicine Consortium;Auer PL;Kooperberg C;Laurie CC;Blackwell TW;Smith AV;Zhao H;Lange E;Lange L;Rich SS;Rotter JI;Wilson JG;Scheet P;Kitzman JO;Lander ES;Engreitz JM;Ebert BL;Reiner AP;Jaiswal S;Abecasis G;Sankaran VG;Kathiresan S;Natarajan P
通讯作者：
Natarajan P
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
DOI：
10.1126/science.aan4673
发表时间：
2019-11-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaiswal S;Ebert BL
通讯作者：
Ebert BL