Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
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DOI：
10.1038/s41588-018-0058-3
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发表时间：
2018-04
期刊：
影响因子：
30.8
通讯作者：
Dichgans M
中科院分区：
文献类型：
--
作者：
Malik R;Chauhan G;Traylor M;Sargurupremraj M;Okada Y;Mishra A;Rutten-Jacobs L;Giese AK;van der Laan SW;Gretarsdottir S;Anderson CD;Chong M;Adams HHH;Ago T;Almgren P;Amouyel P;Ay H;Bartz TM;Benavente OR;Bevan S;Boncoraglio GB;Brown RD Jr;Butterworth AS;Carrera C;Carty CL;Chasman DI;Chen WM;Cole JW;Correa A;Cotlarciuc I;Cruchaga C;Danesh J;de Bakker PIW;DeStefano AL;den Hoed M;Duan Q;Engelter ST;Falcone GJ;Gottesman RF;Grewal RP;Gudnason V;Gustafsson S;Haessler J;Harris TB;Hassan A;Havulinna AS;Heckbert SR;Holliday EG;Howard G;Hsu FC;Hyacinth HI;Ikram MA;Ingelsson E;Irvin MR;Jian X;Jiménez-Conde J;Johnson JA;Jukema JW;Kanai M;Keene KL;Kissela BM;Kleindorfer DO;Kooperberg C;Kubo M;Lange LA;Langefeld CD;Langenberg C;Launer LJ;Lee JM;Lemmens R;Leys D;Lewis CM;Lin WY;Lindgren AG;Lorentzen E;Magnusson PK;Maguire J;Manichaikul A;McArdle PF;Meschia JF;Mitchell BD;Mosley TH;Nalls MA;Ninomiya T;O'Donnell MJ;Psaty BM;Pulit SL;Rannikmäe K;Reiner AP;Rexrode KM;Rice K;Rich SS;Ridker PM;Rost NS;Rothwell PM;Rotter JI;Rundek T;Sacco RL;Sakaue S;Sale MM;Salomaa V;Sapkota BR;Schmidt R;Schmidt CO;Schminke U;Sharma P;Slowik A;Sudlow CLM;Tanislav C;Tatlisumak T;Taylor KD;Thijs VNS;Thorleifsson G;Thorsteinsdottir U;Tiedt S;Trompet S;Tzourio C;van Duijn CM;Walters M;Wareham NJ;Wassertheil-Smoller S;Wilson JG;Wiggins KL;Yang Q;Yusuf S;AFGen Consortium;Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium;International Genomics of Blood Pressure (iGEN-BP) Consortium;INVENT Consortium;STARNET;Bis JC;Pastinen T;Ruusalepp A;Schadt EE;Koplev S;Björkegren JLM;Codoni V;Civelek M;Smith NL;Trégouët DA;Christophersen IE;Roselli C;Lubitz SA;Ellinor PT;Tai ES;Kooner JS;Kato N;He J;van der Harst P;Elliott P;Chambers JC;Takeuchi F;Johnson AD;BioBank Japan Cooperative Hospital Group;COMPASS Consortium;EPIC-CVD Consortium;EPIC-InterAct Consortium;International Stroke Genetics Consortium (ISGC);METASTROKE Consortium;Neurology Working Group of the CHARGE Consortium;NINDS Stroke Genetics Network (SiGN);UK Young Lacunar DNA Study;MEGASTROKE Consortium;Sanghera DK;Melander O;Jern C;Strbian D;Fernandez-Cadenas I;Longstreth WT Jr;Rolfs A;Hata J;Woo D;Rosand J;Pare G;Hopewell JC;Saleheen D;Stefansson K;Worrall BB;Kittner SJ;Seshadri S;Fornage M;Markus HS;Howson JMM;Kamatani Y;Debette S;Dichgans M
中风有多种病因，但潜在的基因和途径在很大程度上是未知的。我们对521，612名个体（67，162例病例和454，450名对照）进行了多祖先全基因组关联荟萃分析，发现了22个新的中风风险位点，使总数达到32个。我们进一步发现了与相关血管性状，包括血压，心脏性状和静脉血栓栓塞症，在个别位点（n = 18），并使用遗传风险评分和连锁不平衡评分回归共享的遗传变异。几个位点表现出不同的关联和多效性模式的病因中风亚型。11个新的易感基因座表明了以前未涉及卒中病理生理学的机制，通过使用广泛的功能数据集进行生物信息学分析，确定了风险变体和基因的优先顺序。抗血栓治疗的药物靶点显著富集卒中风险位点。
Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.
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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：
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
影响因子：
14.9
作者：
Geer LY;Marchler-Bauer A;Geer RC;Han L;He J;He S;Liu C;Shi W;Bryant SH
通讯作者：
Bryant SH
DOI：
10.1126/science.aad6970
发表时间：
2016-08-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franzén O;Ermel R;Cohain A;Akers NK;Di Narzo A;Talukdar HA;Foroughi-Asl H;Giambartolomei C;Fullard JF;Sukhavasi K;Köks S;Gan LM;Giannarelli C;Kovacic JC;Betsholtz C;Losic B;Michoel T;Hao K;Roussos P;Skogsberg J;Ruusalepp A;Schadt EE;Björkegren JL
通讯作者：
Björkegren JL
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium