Clonal hematopoiesis is associated with protection from Alzheimer's disease.
Clonal hematopoiesis is associated with protection from Alzheimer's disease.
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DOI：
10.1038/s41591-023-02397-2
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发表时间：
2023-07
期刊：
影响因子：
82.9
通讯作者：
Jaiswal, Siddhartha
中科院分区：
文献类型：
--
作者：
Bouzid, Hind;Belk, Julia A.;Jan, Max;Qi, Yanyan;Sarnowski, Chloe;Wirth, Sara;Ma, Lisa;Chrostek, Matthew R.;Ahmad, Herra;Nachun, Daniel;Yao, Winnie;Beiser, Alexa;Bick, Alexander G.;Bis, Joshua C.;Fornage, Myriam;Longstreth, William T., Jr.;Lopez, Oscar L.;Natarajan, Pradeep;Psaty, Bruce M.;Satizabal, Claudia L.;Weinstock, Joshua;Larson, Eric B.;Crane, Paul K.;Keene, C. Dirk;Seshadri, Sudha;Satpathy, Ansuman T.;Montine, Thomas J.;Jaiswal, Siddhartha
不确定潜能的克隆性造血（CHIP）是突变的造血干细胞的癌前扩增。由于已知CHIP相关突变会改变骨髓细胞的发育和功能，我们假设CHIP也可能与阿尔茨海默病（AD）的风险相关，这是一种脑驻留骨髓细胞被认为具有主要作用的疾病。为了进行CHIP和AD痴呆之间的关联测试，我们分析了1，362名AD患者和4，368名非AD患者的血液DNA测序数据。CHIP患者患AD痴呆的风险较低（荟萃分析比值比（OR）= 0.64，P = 3.8 × 10−5），孟德尔随机化分析支持潜在的因果关系。我们观察到，在血液中发现的相同突变也在8名CHIP携带者中的7名中的大脑小胶质细胞富集部分中检测到。在六个CHIP携带者的脑源性细胞核的单核染色质可及性分析显示，突变细胞在检查的样品中占小胶质细胞池的很大比例。虽然需要更多的研究来验证机制发现，但这些结果表明CHIP可能在降低AD风险方面发挥作用。在大规模人群队列中，发现不确定潜能的克隆性造血（CHIP）与阿尔茨海默病（AD）的保护作用相关。
Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer’s disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P = 3.8 × 10−5), and Mendelian randomization analyses supported a potential causal association. We observed that the same mutations found in blood were also detected in microglia-enriched fraction of the brain in seven of eight CHIP carriers. Single-nucleus chromatin accessibility profiling of brain-derived nuclei in six CHIP carriers revealed that the mutated cells comprised a large proportion of the microglial pool in the samples examined. While additional studies are required to validate the mechanistic findings, these results suggest that CHIP may have a role in attenuating the risk of AD. Clonal hematopoiesis of indeterminate potential (CHIP) was found to be associated with a protective effect from Alzheimer’s disease (AD) in large population-based cohorts.
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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
在健康个体中预测急性髓样白血病的风险。
影响因子：
64.8
作者：
Abelson S;Collord G;Ng SWK;Weissbrod O;Mendelson Cohen N;Niemeyer E;Barda N;Zuzarte PC;Heisler L;Sundaravadanam Y;Luben R;Hayat S;Wang TT;Zhao Z;Cirlan I;Pugh TJ;Soave D;Ng K;Latimer C;Hardy C;Raine K;Jones D;Hoult D;Britten A;McPherson JD;Johansson M;Mbabaali F;Eagles J;Miller JK;Pasternack D;Timms L;Krzyzanowski P;Awadalla P;Costa R;Segal E;Bratman SV;Beer P;Behjati S;Martincorena I;Wang JCY;Bowles KM;Quirós JR;Karakatsani A;La Vecchia C;Trichopoulou A;Salamanca-Fernández E;Huerta JM;Barricarte A;Travis RC;Tumino R;Masala G;Boeing H;Panico S;Kaaks R;Krämer A;Sieri S;Riboli E;Vineis P;Foll M;McKay J;Polidoro S;Sala N;Khaw KT;Vermeulen R;Campbell PJ;Papaemmanuil E;Minden MD;Tanay A;Balicer RD;Wareham NJ;Gerstung M;Dick JE;Brennan P;Vassiliou GS;Shlush LI
通讯作者：
Shlush LI
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
30.8
作者：
Kar, Siddhartha P.;Quiros, Pedro M.;Gu, Muxin;Jiang, Tao;Mitchell, Jonathan;Langdon, Ryan;Iyer, Vivek;Barcena, Clea;Vijayabaskar, M. S.;Fabre, Margarete A.;Carter, Paul;Petrovski, Slave;Burgess, Stephen;Vassiliou, George S.
通讯作者：
Vassiliou, George S.