Cerebral small vessel disease genomics and its implications across the lifespan.
Cerebral small vessel disease genomics and its implications across the lifespan.
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脑血管疾病基因组学及其在整个生命周期中的意义。
DOI：
10.1038/s41467-020-19111-2
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发表时间：
2020-12-08
影响因子：
16.6
通讯作者：
Debette S
中科院分区：
文献类型：
--
作者：
Sargurupremraj M;Suzuki H;Jian X;Sarnowski C;Evans TE;Bis JC;Eiriksdottir G;Sakaue S;Terzikhan N;Habes M;Zhao W;Armstrong NJ;Hofer E;Yanek LR;Hagenaars SP;Kumar RB;van den Akker EB;McWhirter RE;Trompet S;Mishra A;Saba Y;Satizabal CL;Beaudet G;Petit L;Tsuchida A;Zago L;Schilling S;Sigurdsson S;Gottesman RF;Lewis CE;Aggarwal NT;Lopez OL;Smith JA;Valdés Hernández MC;van der Grond J;Wright MJ;Knol MJ;Dörr M;Thomson RJ;Bordes C;Le Grand Q;Duperron MG;Smith AV;Knopman DS;Schreiner PJ;Evans DA;Rotter JI;Beiser AS;Maniega SM;Beekman M;Trollor J;Stott DJ;Vernooij MW;Wittfeld K;Niessen WJ;Soumaré A;Boerwinkle E;Sidney S;Turner ST;Davies G;Thalamuthu A;Völker U;van Buchem MA;Bryan RN;Dupuis J;Bastin ME;Ames D;Teumer A;Amouyel P;Kwok JB;Bülow R;Deary IJ;Schofield PR;Brodaty H;Jiang J;Tabara Y;Setoh K;Miyamoto S;Yoshida K;Nagata M;Kamatani Y;Matsuda F;Psaty BM;Bennett DA;De Jager PL;Mosley TH;Sachdev PS;Schmidt R;Warren HR;Evangelou E;Trégouët DA;International Network against Thrombosis (INVENT) Consortium;International Headache Genomics Consortium (IHGC);Ikram MA;Wen W;DeCarli C;Srikanth VK;Jukema JW;Slagboom EP;Kardia SLR;Okada Y;Mazoyer B;Wardlaw JM;Nyquist PA;Mather KA;Grabe HJ;Schmidt H;Van Duijn CM;Gudnason V;Longstreth WT Jr;Launer LJ;Lathrop M;Seshadri S;Tzourio C;Adams HH;Matthews PM;Fornage M;Debette S
白质高信号（WMH）是脑小血管疾病（SVD）最常见的脑影像学特征，高血压是已知的主要危险因素。在这里，我们在 50,970 名老年人的队列中确定了 27 个 WMH 体积的全基因组位点，解释了高血压的修改/混杂。在 1,738 名年轻健康成年人的大脑图像中，汇总的 WMH 风险变异与白质完整性的改变 (p = 2.5×10-7) 相关，从而深入了解 SVD 遗传风险的终生影响。孟德尔随机化表明，WMH 容量增加与中风、阿尔茨海默型痴呆以及血压 (BP) 增加与 WMH 容量增加存在因果关系，尤其是在没有临床高血压的人群中。全转录组共定位分析显示 WMH 体积与 39 个基因的表达相关，其中 4 个基因编码已知的药物靶点。最后，我们深入了解了 SVD 背后的与血压无关的生物学途径，并提出了高风险个体的遗传分层和预防试验药物靶点的遗传信息优先级的潜力。白质高信号（WMH）是脑小血管疾病的常见脑影像特征。在这里，作者对 WMH 体积进行了 GWAS 和后续分析，暗示了几种具有风险分层和药物靶向潜力的变异。
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials. White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.
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DOI：
10.1136/bmj.c3666
发表时间：
2010-07-26
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Debette S;Markus HS
通讯作者：
Markus HS
全基因组对言语记忆的言论性记忆的研究：基因组流行病学财团的心脏和衰老研究的同龄人。
影响因子：
10.6
作者：
Debette S;Ibrahim Verbaas CA;Bressler J;Schuur M;Smith A;Bis JC;Davies G;Wolf C;Gudnason V;Chibnik LB;Yang Q;deStefano AL;de Quervain DJ;Srikanth V;Lahti J;Grabe HJ;Smith JA;Priebe L;Yu L;Karbalai N;Hayward C;Wilson JF;Campbell H;Petrovic K;Fornage M;Chauhan G;Yeo R;Boxall R;Becker J;Stegle O;Mather KA;Chouraki V;Sun Q;Rose LM;Resnick S;Oldmeadow C;Kirin M;Wright AF;Jonsdottir MK;Au R;Becker A;Amin N;Nalls MA;Turner ST;Kardia SL;Oostra B;Windham G;Coker LH;Zhao W;Knopman DS;Heiss G;Griswold ME;Gottesman RF;Vitart V;Hastie ND;Zgaga L;Rudan I;Polasek O;Holliday EG;Schofield P;Choi SH;Tanaka T;An Y;Perry RT;Kennedy RE;Sale MM;Wang J;Wadley VG;Liewald DC;Ridker PM;Gow AJ;Pattie A;Starr JM;Porteous D;Liu X;Thomson R;Armstrong NJ;Eiriksdottir G;Assareh AA;Kochan NA;Widen E;Palotie A;Hsieh YC;Eriksson JG;Vogler C;van Swieten JC;Shulman JM;Beiser A;Rotter J;Schmidt CO;Hoffmann W;Nöthen MM;Ferrucci L;Attia J;Uitterlinden AG;Amouyel P;Dartigues JF;Amieva H;Räikkönen K;Garcia M;Wolf PA;Hofman A;Longstreth WT Jr;Psaty BM;Boerwinkle E;DeJager PL;Sachdev PS;Schmidt R;Breteler MM;Teumer A;Lopez OL;Cichon S;Chasman DI;Grodstein F;Müller-Myhsok B;Tzourio C;Papassotiropoulos A;Bennett DA;Ikram MA;Deary IJ;van Duijn CM;Launer L;Fitzpatrick AL;Seshadri S;Mosley TH Jr;Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
通讯作者：
Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
11.2
作者：
Chang, Ansi;Staugaitis, Susan M.;Dutta, Ranjan;Batt, Courtney E.;Easley, Kathryn E.;Chomyk, Anthony M.;Yong, V. Wee;Fox, Robert J.;Kidd, Grahame J.;Trapp, Bruce D.
通讯作者：
Trapp, Bruce D.
影响因子：
64.8
作者：
Ehret, Georg B.;Munroe, Patricia B.;Rice, Kenneth M.;Bochud, Murielle;Johnson, Andrew D.;Chasman, Daniel I.;Smith, Albert V.;Tobin, Martin D.;Verwoert, Germaine C.;Hwang, Shih-Jen;Pihur, Vasyl;Vollenweider, Peter;O'Reilly, Paul F.;Amin, Najaf;Bragg-Gresham, Jennifer L.;Teumer, Alexander;Glazer, Nicole L.;Launer, Lenore;Zhao, Jing Hua;Aulchenko, Yurii;Heath, Simon;Sober, Siim;Parsa, Afshin;Luan, Jian'an;Arora, Pankaj;Dehghan, Abbas;Zhang, Feng;Lucas, Gavin;Hicks, Andrew A.;Jackson, Anne U.;Peden, John F.;Tanaka, Toshiko;Wild, Sarah H.;Rudan, Igor;Igl, Wilmar;Milaneschi, Yuri;Parker, Alex N.;Fava, Cristiano;Chambers, John C.;Fox, Ervin R.;Kumari, Meena;Go, Min Jin;van der Harst, Pim;Kao, Wen Hong Linda;Sjogren, Marketa;Vinay, D. G.;Alexander, Myriam;Tabara, Yasuharu;Shaw-Hawkins, Sue;Whincup, Peter H.;Liu, Yongmei;Shi, Gang;Kuusisto, Johanna;Tayo, Bamidele;Seielstad, Mark;Sim, Xueling;Khanh-Dung Hoang Nguyen;Lehtimaki, Terho;Matullo, Giuseppe;Wu, Ying;Gaunt, Tom R.;Onland-Moret, N. Charlotte;Cooper, Matthew N.;Platou, Carl G. P.;Org, Elin;Hardy, Rebecca;Dahgam, Santosh;Palmen, Jutta;Vitart, Veronique;Braund, Peter S.;Kuznetsova, Tatiana;Uiterwaal, Cuno S. P. M.;Adeyemo, Adebowale;Palmas, Walter;Campbell, Harry;Ludwig, Barbara;Tomaszewski, Maciej;Tzoulaki, Ioanna;Palmer, Nicholette D.;Aspelund, Thor;Garcia, Melissa;Chang, Yen-Pei C.;O'Connell, Jeffrey R.;Steinle, Nanette I.;Grobbee, Diederick E.;Arking, Dan E.;Kardia, Sharon L.;Morrison, Alanna C.;Hernandez, Dena;Najjar, Samer;McArdle, Wendy L.;Hadley, David;Brown, Morris J.;Connell, John M.;Hingorani, Aroon D.;Day, Ian N. M.;Lawlor, Debbie A.;Beilby, John P.;Lawrence, Robert W.;Clarke, Robert;Hopewell, Jemma C.;Ongen, Halit;Dreisbach, Albert W.;Li, Yali;Young, J. Hunter;Bis, Joshua C.;Kahonen, Mika;Viikari, Jorma;Adair, Linda S.;Lee, Nanette R.;Chen, Ming-Huei;Olden, Matthias;Pattaro, Cristian;Bolton, Judith A. Hoffman;Koettgen, Anna;Bergmann, Sven;Mooser, Vincent;Chaturvedi, Nish;Frayling, Timothy M.;Islam, Muhammad;Jafar, Tazeen H.;Erdmann, Jeanette;Kulkarni, Smita R.;Bornstein, Stefan R.;Graessler, Juergen;Groop, Leif;Voight, Benjamin F.;Kettunen, Johannes;Howard, Philip;Taylor, Andrew;Guarrera, Simonetta;Ricceri, Fulvio;Emilsson, Valur;Plump, Andrew;Barroso, Ine S.;Khaw, Kay-Tee;Weder, Alan B.;Hunt, Steven C.;Sun, Yan V.;Bergman, Richard N.;Collins, Francis S.;Bonnycastle, Lori L.;Scott, Laura J.;Stringham, Heather M.;Peltonen, Leena;Perola, Markus;Vartiainen, Erkki;Brand, Stefan-Martin;Staessen, Jan A.;Wang, Thomas J.;Burton, Paul R.;Artigas, Maria Soler;Dong, Yanbin;Snieder, Harold;Wang, Xiaoling;Zhu, Haidong;Lohman, Kurt K.;Rudock, Megan E.;Heckbert, Susan R.;Smith, Nicholas L.;Wiggins, Kerri L.;Doumatey, Ayo;Shriner, Daniel;Veldre, Gudrun;Viigimaa, Margus;Kinra, Sanjay;Prabhakaran, Dorairaj;Tripathy, Vikal;Langefeld, Carl D.;Rosengren, Annika;Thelle, Dag S.;Corsi, Anna Maria;Singleton, Andrew;Forrester, Terrence;Hilton, Gina;McKenzie, Colin A.;Salako, Tunde;Iwai, Naoharu;Kita, Yoshikuni;Ogihara, Toshio;Ohkubo, Takayoshi;Okamura, Tomonori;Ueshima, Hirotsugu;Umemura, Satoshi;Eyheramendy, Susana;Meitinger, Thomas;Wichmann, H. -Erich;Cho, Yoon Shin;Kim, Hyung-Lae;Lee, Jong-Young;Scott, James;Sehmi, Joban S.;Zhang, Weihua;Hedblad, Bo;Nilsson, Peter;Smith, George Davey;Wong, Andrew;Narisu, Narisu;Stancakova, Alena;Raffel, Leslie J.;Yao, Jie;Kathiresan, Sekar;O'Donnell, Christopher J.;Schwartz, Stephen M.;Ikram, M. Arfan;Longstreth, W. T., Jr.;Mosley, Thomas H.;Seshadri, Sudha;Shrine, Nick R. G.;Wain, Louise V.;Morken, Mario A.;Swift, Amy J.;Laitinen, Jaana;Prokopenko, Inga;Zitting, Paavo;Cooper, Jackie A.;Humphries, Steve E.;Danesh, John;Rasheed, Asif;Goel, Anuj;Hamsten, Anders;Watkins, Hugh;Bakker, Stephan J. L.;van Gilst, Wiek H.;Janipalli, Charles S.;Mani, K. Radha;Yajnik, Chittaranjan S.;Hofman, Albert;Mattace-Raso, Francesco U. S.;Oostra, Ben A.;Demirkan, Ayse;Isaacs, Aaron;Rivadeneira, Fernando;Lakatta, Edward G.;Orru, Marco;Scuteri, Angelo;Ala-Korpela, Mika;Kangas, Antti J.;Lyytikainen, Leo-Pekka;Soininen, Pasi;Tukiainen, Taru;Wurtz, Peter;Ong, Rick Twee-Hee;Doerr, Marcus;Kroemer, Heyo K.;Voelker, Uwe;Voelzke, Henry;Galan, Pilar;Hercberg, Serge;Lathrop, Mark;Zelenika, Diana;Deloukas, Panos;Mangino, Massimo;Spector, Tim D.;Zhai, Guangju;Meschia, James F.;Nalls, Michael A.;Sharma, Pankaj;Terzic, Janos;Kumar, M. V. Kranthi;Denniff, Matthew;Zukowska-Szczechowska, Ewa;Wagenknecht, Lynne E.;Fowkes, F. Gerald R.;Charchar, Fadi J.;Schwarz, Peter E. H.;Hayward, Caroline;Guo, Xiuqing;Rotimi, Charles;Bots, Michiel L.;Brand, Eva;Samani, Nilesh J.;Polasek, Ozren;Talmud, Philippa J.;Nyberg, Fredrik;Kuh, Diana;Laan, Maris;Hveem, Kristian;Palmer, Lyle J.;van der Schouw, Yvonne T.;Casas, Juan P.;Mohlke, Karen L.;Vineis, Paolo;Raitakari, Olli;Ganesh, Santhi K.;Wong, Tien Y.;Tai, E. Shyong;Cooper, Richard S.;Laakso, Markku;Rao, Dabeeru C.;Harris, Tamara B.;Morris, Richard W.;Dominiczak, Anna F.;Kivimaki, Mika;Marmot, Michael G.;Miki, Tetsuro;Saleheen, Danish;Chandak, Giriraj R.;Coresh, Josef;Navis, Gerjan;Salomaa, Veikko;Han, Bok-Ghee;Zhu, Xiaofeng;Kooner, Jaspal S.;Melander, Olle;Ridker, Paul M.;Bandinelli, Stefania;Gyllensten, Ulf B.;Wright, Alan F.;Wilson, James F.;Ferrucci, Luigi;Farrall, Martin;Tuomilehto, Jaakko;Pramstaller, Peter P.;Elosua, Roberto;Soranzo, Nicole;Sijbrands, Eric J. G.;Altshuler, David;Loos, Ruth J. F.;Shuldiner, Alan R.;Gieger, Christian;Meneton, Pierre;Uitterlinden, Andre G.;Wareham, Nicholas J.;Gudnason, Vilmundur;Rotter, Jerome I.;Rettig, Rainer;Uda, Manuela;Strachan, David P.;Witteman, Jacqueline C. M.;Hartikainen, Anna-Liisa;Beckmann, Jacques S.;Boerwinkle, Eric;Vasan, Ramachandran S.;Boehnke, Michael;Larson, Martin G.;Jarvelin, Marjo-Riitta;Psaty, Bruce M.;Abecasis, Goncalo R.;Chakravarti, Aravinda;Elliott, Paul;van Duijn, Cornelia M.;Newton-Cheh, Christopher;Levy, Daniel;Caulfield, Mark J.;Johnson, Toby
通讯作者：
Johnson, Toby