Causal Associations Between Modifiable Risk Factors and the Alzheimer's Phenome.
Causal Associations Between Modifiable Risk Factors and the Alzheimer's Phenome.
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DOI：
10.1002/ana.25918
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发表时间：
2021-01
影响因子：
11.2
通讯作者：
collaborators of the Alzheimer's Disease Genetics Consortium
中科院分区：
文献类型：
--
作者：
Andrews SJ;Fulton-Howard B;O'Reilly P;Marcora E;Goate AM;collaborators of the Alzheimer's Disease Genetics Consortium
这项研究的目的是推断22个先前报道的阿尔茨海默病(AD)危险因素与AD现象组之间的因果关系：AD、AD发病年龄、海马体积、皮质表面积和厚度、脑脊液中淀粉样蛋白β(Aβ42)、tau和ptau181水平，以及神经炎斑块、神经原纤维缠结(NFT)和血管脑损伤(VBI)的神经病理负担。在26,431例AD患者/对照中计算了22个危险因素的多基因风险分数(PR)，并用Logistic回归分析了其与AD的相关性。采用两样本孟德尔随机化(MR)方法推断危险因素对AD表型的因果效应。增加教育程度和舒张压的PR与AD风险降低相关。MR指出，只有教育与AD风险降低、AAOS延迟、皮质表面积和厚度增加存在因果关系。总胆固醇和低密度脂蛋白-胆固醇水平与神经炎斑块负荷增加有因果关系，尽管这种影响是由APOE基因座内的单核苷酸多态(SNPs)驱动的。舒张压和脉压与VBI风险增加有因果关系。此外，总胆固醇与海马体体积减少、开始吸烟与皮质厚度减少、2型糖尿病早期AAOS以及睡眠时间与皮质厚度增加有关。我们使用PRS和MR对先前报道的AD风险因素之间的因果关系的遗传证据进行了全面的研究，支持教育、血压、胆固醇水平、吸烟和糖尿病与AD现象之间的因果关系。
The purpose of this study was to infer causal relationships between 22 previously reported risk factors for Alzheimer’s disease (AD) and the “AD phenome”: AD, AD age of onset (AAOS), hippocampal volume, cortical surface area and thickness, cerebrospinal fluid (CSF) levels of amyloid-β (Aβ42), tau, and ptau181, and the neuropathological burden of neuritic plaques, neurofibrillary tangles (NFTs), and vascular brain injury (VBI). Polygenic risk scores (PRS) for the 22 risk factors were computed in 26,431 AD cases/controls and the association with AD was evaluated using logistic regression. Two-sample Mendelian randomization (MR) was used to infer the causal effect of risk factors on the AD phenome. PRS for increased education and diastolic blood pressure were associated with reduced risk for AD. MR indicated that only education was causally associated with reduced risk of AD, delayed AAOS, and increased cortical surface area and thickness. Total- and LDL-cholesterol levels were causally associated with increased neuritic plaque burden, although the effects were driven by single nucleotide polymorphisms (SNPs) within the APOE locus. Diastolic blood pressure and pulse pressure are causally associated with increased risk of VBI. Furthermore, total cholesterol was associated with decreased hippocampal volume; smoking initiation with decreased cortical thickness; type 2 diabetes with an earlier AAOS; and sleep duration with increased cortical thickness. Our comprehensive examination of the genetic evidence for the causal relationships between previously reported risk factors in AD using PRS and MR supports a causal role for education, blood pressure, cholesterol levels, smoking, and diabetes with the AD phenome.
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与海马体积相关的新型遗传基因座。
影响因子：
16.6
作者：
Hibar DP;Adams HHH;Jahanshad N;Chauhan G;Stein JL;Hofer E;Renteria ME;Bis JC;Arias-Vasquez A;Ikram MK;Desrivières S;Vernooij MW;Abramovic L;Alhusaini S;Amin N;Andersson M;Arfanakis K;Aribisala BS;Armstrong NJ;Athanasiu L;Axelsson T;Beecham AH;Beiser A;Bernard M;Blanton SH;Bohlken MM;Boks MP;Bralten J;Brickman AM;Carmichael O;Chakravarty MM;Chen Q;Ching CRK;Chouraki V;Cuellar-Partida G;Crivello F;Den Braber A;Doan NT;Ehrlich S;Giddaluru S;Goldman AL;Gottesman RF;Grimm O;Griswold ME;Guadalupe T;Gutman BA;Hass J;Haukvik UK;Hoehn D;Holmes AJ;Hoogman M;Janowitz D;Jia T;Jørgensen KN;Karbalai N;Kasperaviciute D;Kim S;Klein M;Kraemer B;Lee PH;Liewald DCM;Lopez LM;Luciano M;Macare C;Marquand AF;Matarin M;Mather KA;Mattheisen M;McKay DR;Milaneschi Y;Muñoz Maniega S;Nho K;Nugent AC;Nyquist P;Loohuis LMO;Oosterlaan J;Papmeyer M;Pirpamer L;Pütz B;Ramasamy A;Richards JS;Risacher SL;Roiz-Santiañez R;Rommelse N;Ropele S;Rose EJ;Royle NA;Rundek T;Sämann PG;Saremi A;Satizabal CL;Schmaal L;Schork AJ;Shen L;Shin J;Shumskaya E;Smith AV;Sprooten E;Strike LT;Teumer A;Tordesillas-Gutierrez D;Toro R;Trabzuni D;Trompet S;Vaidya D;Van der Grond J;Van der Lee SJ;Van der Meer D;Van Donkelaar MMJ;Van Eijk KR;Van Erp TGM;Van Rooij D;Walton E;Westlye LT;Whelan CD;Windham BG;Winkler AM;Wittfeld K;Woldehawariat G;Wolf C;Wolfers T;Yanek LR;Yang J;Zijdenbos A;Zwiers MP;Agartz I;Almasy L;Ames D;Amouyel P;Andreassen OA;Arepalli S;Assareh AA;Barral S;Bastin ME;Becker DM;Becker JT;Bennett DA;Blangero J;van Bokhoven H;Boomsma DI;Brodaty H;Brouwer RM;Brunner HG;Buckner RL;Buitelaar JK;Bulayeva KB;Cahn W;Calhoun VD;Cannon DM;Cavalleri GL;Cheng CY;Cichon S;Cookson MR;Corvin A;Crespo-Facorro B;Curran JE;Czisch M;Dale AM;Davies GE;De Craen AJM;De Geus EJC;De Jager PL;De Zubicaray GI;Deary IJ;Debette S;DeCarli C;Delanty N;Depondt C;DeStefano A;Dillman A;Djurovic S;Donohoe G;Drevets WC;Duggirala R;Dyer TD;Enzinger C;Erk S;Espeseth T;Fedko IO;Fernández G;Ferrucci L;Fisher SE;Fleischman DA;Ford I;Fornage M;Foroud TM;Fox PT;Francks C;Fukunaga M;Gibbs JR;Glahn DC;Gollub RL;Göring HHH;Green RC;Gruber O;Gudnason V;Guelfi S;Håberg AK;Hansell NK;Hardy J;Hartman CA;Hashimoto R;Hegenscheid K;Heinz A;Le Hellard S;Hernandez DG;Heslenfeld DJ;Ho BC;Hoekstra PJ;Hoffmann W;Hofman A;Holsboer F;Homuth G;Hosten N;Hottenga JJ;Huentelman M;Hulshoff Pol HE;Ikeda M;Jack CR Jr;Jenkinson M;Johnson R;Jönsson EG;Jukema JW;Kahn RS;Kanai R;Kloszewska I;Knopman DS;Kochunov P;Kwok JB;Lawrie SM;Lemaître H;Liu X;Longo DL;Lopez OL;Lovestone S;Martinez O;Martinot JL;Mattay VS;McDonald C;McIntosh AM;McMahon FJ;McMahon KL;Mecocci P;Melle I;Meyer-Lindenberg A;Mohnke S;Montgomery GW;Morris DW;Mosley TH;Mühleisen TW;Müller-Myhsok B;Nalls MA;Nauck M;Nichols TE;Niessen WJ;Nöthen MM;Nyberg L;Ohi K;Olvera RL;Ophoff RA;Pandolfo M;Paus T;Pausova Z;Penninx BWJH;Pike GB;Potkin SG;Psaty BM;Reppermund S;Rietschel M;Roffman JL;Romanczuk-Seiferth N;Rotter JI;Ryten M;Sacco RL;Sachdev PS;Saykin AJ;Schmidt R;Schmidt H;Schofield PR;Sigursson S;Simmons A;Singleton A;Sisodiya SM;Smith C;Smoller JW;Soininen H;Steen VM;Stott DJ;Sussmann JE;Thalamuthu A;Toga AW;Traynor BJ;Troncoso J;Tsolaki M;Tzourio C;Uitterlinden AG;Hernández MCV;Van der Brug M;van der Lugt A;van der Wee NJA;Van Haren NEM;van 't Ent D;Van Tol MJ;Vardarajan BN;Vellas B;Veltman DJ;Völzke H;Walter H;Wardlaw JM;Wassink TH;Weale ME;Weinberger DR;Weiner MW;Wen W;Westman E;White T;Wong TY;Wright CB;Zielke RH;Zonderman AB;Martin NG;Van Duijn CM;Wright MJ;Longstreth WT;Schumann G;Grabe HJ;Franke B;Launer LJ;Medland SE;Seshadri S;Thompson PM;Ikram MA
通讯作者：
Ikram MA
影响因子：
16.6
作者：
Day FR;Ong KK;Perry JRB
通讯作者：
Perry JRB
DOI：
10.1038/s41366-018-0120-3
发表时间：
2018-06
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Klimentidis YC;Raichlen DA;Bea J;Garcia DO;Wineinger NE;Mandarino LJ;Alexander GE;Chen Z;Going SB
通讯作者：
Going SB
影响因子：
2.1
作者：
Conomos MP;Miller MB;Thornton TA
通讯作者：
Thornton TA
影响因子：
14
作者：
通讯作者：
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