Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

doi:10.1038/s41588-020-00713-x

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24945

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题名:	Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
作者:	Surendran, P;Feofanova, EV;Lahrouchi, N;Ntalla, I;Karthikeyan, S;Cook, J;Chen, LY;Mifsud, B;Yao, C;Kraja, AT;Cartwright, JH;Hellwege, JN;Giri, A;Tragante, V;Thorleifsson, G;Liu, DJJ;Prins, BP;Stewart, ID;Cabrera, CP;Eales, JM;Akbarov, A;Auer, PL;Bielak, LF;Bis, JC;Braithwaite, VS;Brody, JA;Daw, EW;Warren, HR;Drenos, F;Nielsen, SF;Faul, JD;Fauman, EB;Fava, C;Ferreira, T;Foley, CN;Franceschini, N;Gao, H;Giannakopoulou, O;Giulianini, F;Gudbjartsson, DF;Guo, XQ;Harris, SE;Havulinna, AS;Helgadottir, A;Huffman, JE;Hwang, SJ;Kanoni, S;Kontto, J;Larson, MG;Li-Gao, R;Lindstrom, J;Lotta, LA;Lu, YC;Luan, JA;Mahajan, A;Malerba, G;Masca, NGD;Mei, H;Menni, C;Mook-Kanamori, DO;Mosen-Ansorena, D;Muller-Nurasyid, M;Pare, G;Paul, DS;Perola, M;Poveda, A;Rauramaa, R;Richard, M;Richardson, TG;Sepulveda, N;Sim, XL;Smith, AV;Smith, JA;Staley, JR;Stanakova, A;Sulem, P;Theriault, S;Thorsteinsdottir, U;Trompet, S;Varga, TV;Edwards, DRV;Veronesi, G;Weiss, S;Willems, SM;Yao, J;Young, RB;Yu, B;Zhang, WH;Zhao, JH;Zhao, W;Zhao, W;Evangelou, E;Aeschbacher, S;Asllanaj, E;Blankenberg, S;Bonnycastle, LL;Bork-Jensen, J;Brandslund, I;Braund, PS;Burgess, S;Cho, K;Christensen, C;Connell, J;de Mutsert, R;Dominiczak, AF;Dorr, M;Eiriksdottir, G;Farmaki, AE;Gaziano, JM;Grarup, N;Grove, ML;Hallmans, G;Hansen, T;Have, CT;Heiss, G;Jorgensen, ME;Jousilahti, P;Kajantie, E;Kamat, M;Karajamaki, A;Karpe, F;Koistinen, HA;Kovesdy, CP;Kuulasmaa, K;Laatikainen, T;Lannfelt, L;Lee, IT;Lee, WJ;Linneberg, A;Martin, LW;Moitry, M;Nadkarni, G;Neville, MJ;Palmer, CNA;Papanicolaou, GJ;Pedersen, O;Peters, J;Poulter, N;Rasheed, A;Rasmussen, KL;Rayner, NW;Magi, R;Renstrom, F;Rettig, R;Rossouw, J;Schreiner, PJ;Sever, PS;Sigurdsson, EL;Skaaby, T;Sun, YV;Sundstrom, J;Thorgeirsson, G;Esko, T;Trabetti, E;Tsao, PS;Tuomi, T;Turner, ST;Tzoulaki, I;Vaartjes, I;Vergnaud, AC;Willer, CJ;Wilson, PWF;Witte, DR;Yonova-Doing, E;Zhang, H;Aliya, N;Almgren, P;Amouyel, P;Asselbergs, FW;Barnes, MR;Blakemore, AI;Boehnke, M;Bots, ML;Bottinger, EP;Buring, JE;Chambers, JC;Chen, YDI;Chowdhury, R;Conen, D;Correa, A;Smith, GD;de Boer, RA;Deary, IJ;Dedoussis, G;Deloukas, P;Di Angelantonio, E;Elliott, P;Felix, SB;Ferrieres, J;Ford, I;Fornage, M;Franks, PW;Franks, S;Frossard, P;Gambaro, G;Gaunt, TR;Groop, L;Gudnason, V;Harris, TB;Hayward, C;Hennig, BJ;Herzig, KH;Ingelsson, E;Tuomilehto, J;Jarvelin, MR;Jukema, JW;Kardia, SLR;Kee, F;Kooner, JS;Kooperberg, C;Launer, LJ;Lind, L;Loos, RJF;Majumder, AA;Laakso, M;McCarthy, MI;Melander, O;Mohlke, KL;Murray, AD;Nordestgaard, BG;Orho-Melander, M;Packard, CJ;Padmanabhan, S;Palmas, W;Polasek, O;Porteous, DJ;Prentice, AM;Province, MA;Relton, CL;Rice, K;Ridker, PM;Rolandsson, O;Rosendaal, FR;Rotter, JI;Rudan, I;Salomaa, V;Samani, NJ;Sattar, N;Sheu, WHH;Smith, BH;Soranzo, N;Spector, TD;Starr, JM;Sebert, S;Taylor, KD;Lakka, TA;Timpson, NJ;Tobin, MD;van der Harst, P;van der Meer, P;Ramachandran, VS;Verweij, N;Virtamo, J;Volker, U;Weir, DR;Zeggini, E;Charchar, FJ;Wareham, NJ;Langenberg, C;Tomaszewski, M;Butterworth, AS;Caulfield, MJ;Danesh, J;Edwards, TL;Holm, H;Hung, AM;Lindgren, CM;Liu, CY;Manning, AK;Morris, AP;Morrison, AC;O'Donnell, CJ;Psaty, BM;Saleheen, D;Stefansson, K;Boerwinkle, E;Chasman, DI;Levy, D;Newton-Cheh, C;Munroe, PB;Howson, JMM
日期:	2020
上传时间:	2022-08-09T08:10:40Z (UTC)
出版者:	NATURE RESEARCH
ISSN:	1061-4036
摘要:	Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
URI:	http://dx.doi.org/10.1038/s41588-020-00713-x https://www.webofscience.com/wos/woscc/full-record/WOS:000592028900001 https://ir.csmu.edu.tw:8080/handle/310902500/24945
關聯:	NATURE GENETICS ,2020 ,v52 ,issue 12 ,p1314-1332
显示于类别:	[中山醫學大學研究成果] 期刊論文

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