Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels.
Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels.
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DOI：
10.1038/s42003-022-03287-y
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发表时间：
2022-04-08
影响因子：
5.9
通讯作者：
Seshadri S
中科院分区：
文献类型：
--
作者：
Sarnowski C;Ghanbari M;Bis JC;Logue M;Fornage M;Mishra A;Ahmad S;Beiser AS;Boerwinkle E;Bouteloup V;Chouraki V;Cupples LA;Damotte V;DeCarli CS;DeStefano AL;Djoussé L;Fohner AE;Franz CE;Kautz TF;Lambert JC;Lyons MJ;Mosley TH;Mukamal KJ;Pase MP;Portilla Fernandez EC;Rissman RA;Satizabal CL;Vasan RS;Yaqub A;Debette S;Dufouil C;Launer LJ;Kremen WS;Longstreth WT;Ikram MA;Seshadri S
循环总tau水平可用作内表型以鉴定tau蛋白病和相关神经病症的遗传风险因素。在这里，我们在14,721名欧洲参与者中证实并更好地描述了17 q21 MAPT基因座与循环总tau的关联，并在953名非洲裔美国参与者中确定了三个新的基因座（4 q31，5 p13和6 q25），P < 5 × 10−8。我们还在P < 5 × 10−7时检测到了14个新的基因座，这些基因座是欧洲人或非洲裔美国人特有的。使用2，279名欧洲参与者的全外显子组序列数据，我们在聚集罕见变体时确定了与循环总tau相关的10个基因。我们的遗传学研究揭示了与神经系统疾病相关的基因，包括中风，阿尔茨海默氏症和帕金森氏症（F5，MAP 1B和BCAS 3），具有阿尔茨海默病的病理标志（ADAMTS 12、IL 15和FHIT），或在大脑中具有重要功能（PARD 3，ELFN 2，UBASH 3B，SLIT 3和NSD 3），并表明循环总tau的遗传结构可能根据祖先而不同。循环总tau水平的全基因组关联研究的荟萃分析确定了欧洲或非洲裔美国人祖先特有的基因座，为神经系统疾病的遗传病因学提供了进一步的见解。
Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21 MAPT locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American participants (4q31, 5p13, and 6q25) at P < 5 × 10−8. We additionally detected 14 novel loci at P < 5 × 10−7, specific to either Europeans or African Americans. Using whole-exome sequence data in 2,279 European participants, we identified ten genes associated with circulating total-tau when aggregating rare variants. Our genetic study sheds light on genes reported to be associated with neurological diseases including stroke, Alzheimer’s, and Parkinson’s (F5, MAP1B, and BCAS3), with Alzheimer’s pathological hallmarks (ADAMTS12, IL15, and FHIT), or with an important function in the brain (PARD3, ELFN2, UBASH3B, SLIT3, and NSD3), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry. A meta-analysis of genome-wide association studies of circulating total-tau levels identifies loci specific to European or African American ancestries, providing further insight to the genetic etiology of neurological diseases.
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影响因子：
4.8
作者：
Jensen, PH;Islam, K;Gai, WP
通讯作者：
Gai, WP
影响因子：
11.8
作者：
Chen, She;Chen, Jia;Shi, Hang;Wei, Michelle;Castaneda-Castellanos, David R.;Bultje, Ronald S.;Pei, Xin;Kriegstein, Arnold R.;Zhang, Mingjie;Shi, Song-Hai
通讯作者：
Shi, Song-Hai
影响因子：
64.5
作者：
Brose, K;Bland, KS;Kidd, T
通讯作者：
Kidd, T
影响因子：
64.8
作者：
Hibar, Derrek P.;Stein, Jason L.;Renteria, Miguel E.;Arias-Vasquez, Alejandro;Desrivieres, Sylvane;Jahanshad, Neda;Toro, Roberto;Wittfeld, Katharina;Abramovic, Lucija;Andersson, Micael;Aribisala, Benjamin S.;Armstrong, Nicola J.;Bernard, Manon;Bohlken, Marc M.;Boks, Marco P.;Bralten, Janita;Brown, Andrew A.;Chakravarty, M. Mallar;Chen, Qiang;Ching, Christopher R. K.;Cuellar-Partida, Gabriel;den Braber, Anouk;Giddaluru, Sudheer;Goldman, Aaron L.;Grimm, Oliver;Guadalupe, Tulio;Hass, Johanna;Woldehawariat, Girma;Holmes, Avram J.;Hoogman, Martine;Janowitz, Deborah;Jia, Tianye;Kim, Sungeun;Klein, Marieke;Kraemer, Bernd;Lee, Phil H.;Loohuis, Loes M. Olde;Luciano, Michelle;Macare, Christine;Mather, Karen A.;Mattheisen, Manuel;Milaneschi, Yuri;Nho, Kwangsik;Papmeyer, Martina;Ramasamy, Adaikalavan;Risacher, Shannon L.;Roiz-Santianez, Roberto;Rose, Emma J.;Salami, Alireza;Saemann, Philipp G.;Schmaal, Lianne;Schork, Andrew J.;Shin, Jean;Strike, Lachlan T.;Teumer, Alexander;van Donkelaar, Marjolein M. J.;van Eijk, Kristel R.;Walters, Raymond K.;Westlye, Lars T.;Whelan, Christopher D.;Winkler, Anderson M.;Zwiers, Marcel P.;Alhusaini, Saud;Athanasiu, Lavinia;Ehrlich, Stefan;Hakobjan, Marina M. H.;Hartberg, Cecilie B.;Haukvik, Unn K.;Heister, Angelien J. G. A. M.;Hoehn, David;Kasperaviciute, Dalia;Liewald, David C. M.;Lopez, Lorna M.;Makkinje, Remco R. R.;Matarin, Mar;Naber, Marlies A. M.;McKay, D. Reese;Needham, Margaret;Nugent, Allison C.;Puetz, Benno;Royle, Natalie A.;Shen, Li;Sprooten, Emma;Trabzuni, Daniah;van der Marel, Saskia S. L.;van Hulzen, Kimm J. E.;Walton, Esther;Wolf, Christiane;Almasy, Laura;Ames, David;Arepalli, Sampath;Assareh, Amelia A.;Bastin, Mark E.;Brodaty, Henry;Bulayeva, Kazima B.;Carless, Melanie A.;Cichon, Sven;Corvin, Aiden;Curran, Joanne E.;Czisch, Michael;de Zubicaray, Greig I.;Dillman, Allissa;Duggirala, Ravi;Dyer, Thomas D.;Erk, Susanne;Fedko, Iryna O.;Ferrucci, Luigi;Foroud, Tatiana M.;Fox, Peter T.;Fukunaga, Masaki;Gibbs, J. Raphael;Goering, Harald H. H.;Green, Robert C.;Guelfi, Sebastian;Hansell, Narelle K.;Hartman, Catharina A.;Hegenscheid, Katrin;Heinz, Andreas;Hernandez, Dena G.;Heslenfeld, Dirk J.;Hoekstra, Pieter J.;Holsboer, Florian;Homuth, Georg;Hottenga, Jouke-Jan;Ikeda, Masashi;Jack, Clifford R., Jr.;Jenkinson, Mark;Johnson, Robert;Kanai, Ryota;Keil, Maria;Kent, Jack W., Jr.;Kochunov, Peter;Kwok, John B.;Lawrie, Stephen M.;Liu, Xinmin;Longo, Dan L.;McMahon, Katie L.;Meisenzah, Eva;Melle, Ingrid;Mahnke, Sebastian;Montgomery, Grant W.;Mostert, Jeanette C.;Muehleisen, Thomas W.;Nalls, Michael A.;Nichols, Thomas E.;Nilsson, Lars G.;Noethen, Markus M.;Ohi, Kazutaka;Olvera, Rene L.;Perez-Iglesias, Rocio;Pike, G. Bruce;Potkin, Steven G.;Reinvang, Ivar;Reppermund, Simone;Rietschel, Marcella;Romanczuk-Seiferth, Nina;Rosen, Glenn D.;Rujescu, Dan;Schnell, Knut;Schofield, Peter R.;Smith, Colin;Steen, Vidar M.;Sussmann, Jessika E.;Thalamuthu, Anbupalam;Toga, Arthur W.;Traynor, Bryan J.;Troncoso, Juan;Turner, Jessica A.;Valdes Hernandez, Maria C.;van't Ent, Dennis;van der Brug, Marcel;van der Wee, Nic J. A.;van Tol, Marie-Jose;Veltman, Dick J.;Wassink, Thomas H.;Westman, Eric;Zielke, Ronald H.;Zonderman, Alan B.;Ashbrook, David G.;Hager, Reinmar;Lu, Lu;McMahon, Francis J.;Morris, Derek W.;Williams, Robert W.;Brunner, Han G.;Buckner, Randy L.;Buitelaar, Jan K.;Cahn, Wiepke;Calhoun, Vince D.;Cavalleri, Gianpiero L.;Crespo-Facorro, Benedicto;Dale, Anders M.;Davies, Gareth E.;Delanty, Norman;Depondt, Chantal;Djurovic, Srdjan;Drevets, Wayne C.;Espeseth, Thomas;Gollub, Randy L.;Ho, Beng-Choon;Hoffman, Wolfgang;Hosten, Norbert;Kahn, Rene S.;Le Hellard, Stephanie;Meyer-Lindenberg, Andreas;Mueller-Myhsok, Bertram;Nauck, Matthias;Nyberg, Lars;Pandolfo, Massimo;Penninx, Brenda W. J. H.;Roffman, Joshua L.;Sisodiya, Sanjay M.;Smoller, Jordan W.;van Bokhoven, Hans;van Haren, Neeltje E. M.;Voelzke, Henry;Walter, Henrik;Weiner, Michael W.;Wen, Wei;White, Tonya;Agartz, Ingrid;Andreassen, Ole A.;Blangero, John;Boomsma, Dorret I.;Brouwer, Rachel M.;Cannon, Dara M.;Cookson, Mark R.;de Geus, Eco J. C.;Deary, Ian J.;Donohoe, Gary;Fernandez, Guillen;Fisher, Simon E.;Francks, Clyde;Glahn, David C.;Grabe, Hans J.;Gruber, Oliver;Hardy, John;Hashimoto, Ryota;Pol, Hilleke E. Hulshoff;Joensson, Erik G.;Kloszewska, Iwona;Lovestone, Simon;Mattay, Venkata S.;Mecocci, Patrizia;McDonald, Colm;McIntosh, Andrew M.;Ophoff, Roel A.;Paus, Tomas;Pausova, Zdenka;Ryten, Mina;Sachdev, Perminder S.;Saykin, Andrew J.;Simmons, Andy;Singleton, Andrew;Soininen, Hilkka;Wardlaw, Joanna M.;Weale, Michael E.;Weinberger, Daniel R.;Adams, Hieab H. H.;Launer, Lenore J.;Seiler, Stephan;Schmidt, Reinhold;Chauhan, Ganesh;Satizabal, Claudia L.;Becker, James T.;Yanek, Lisa;van der Lee, Sven J.;Ebling, Maritza;Fischl, Bruce;Longstreth, W. T., Jr.;Greve, Douglas;Schmidt, Helena;Nyquist, Paul;Vinke, Louis N.;van Duijn, Cornelia M.;Xue, Luting;Mazoyer, Bernard;Bis, Joshua C.;Gudnason, Vilmundur;Seshadri, Sudha;Ikram, M. Arfan;Martin, Nicholas G.;Wright, Margaret J.;Schumann, Gunter;Franke, Barbara;Thompson, Paul M., Jr.;Medland, Sarah E.
通讯作者：
Medland, Sarah E.
影响因子：
9.3
作者：
Das A;Kim SH;Arifuzzaman S;Yoon T;Chai JC;Lee YS;Park KS;Jung KH;Chai YG
通讯作者：
Chai YG