Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
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DOI：
10.1038/s41588-020-00713-x
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发表时间：
2020-12
期刊：
影响因子：
30.8
通讯作者：
Howson JMM
中科院分区：
文献类型：
--
作者：
Surendran P;Feofanova EV;Lahrouchi N;Ntalla I;Karthikeyan S;Cook J;Chen L;Mifsud B;Yao C;Kraja AT;Cartwright JH;Hellwege JN;Giri A;Tragante V;Thorleifsson G;Liu DJ;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 X;Harris SE;Havulinna AS;Helgadottir A;Huffman JE;Hwang SJ;Kanoni S;Kontto J;Larson MG;Li-Gao R;Lindström J;Lotta LA;Lu Y;Luan J;Mahajan A;Malerba G;Masca NGD;Mei H;Menni C;Mook-Kanamori DO;Mosen-Ansorena D;Müller-Nurasyid M;Paré G;Paul DS;Perola M;Poveda A;Rauramaa R;Richard M;Richardson TG;Sepúlveda N;Sim X;Smith AV;Smith JA;Staley JR;Stanáková A;Sulem P;Thériault S;Thorsteinsdottir U;Trompet S;Varga TV;Velez Edwards DR;Veronesi G;Weiss S;Willems SM;Yao J;Young R;Yu B;Zhang W;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;Mutsert R;Dominiczak AF;Dörr M;Eiriksdottir G;Farmaki AE;Gaziano JM;Grarup N;Grove ML;Hallmans G;Hansen T;Have CT;Heiss G;Jørgensen ME;Jousilahti P;Kajantie E;Kamat M;Käräjämäki A;Karpe F;Koistinen HA;Kovesdy CP;Kuulasmaa K;Laatikainen T;Lannfelt L;Lee IT;Lee WJ;LifeLines Cohort Study;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;Mägi R;Renström 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 YI;Chowdhury R;Conen D;Correa A;Davey Smith G;Boer RA;Deary IJ;Dedoussis G;Deloukas P;Di Angelantonio E;Elliott P;EPIC-CVD;EPIC-InterAct;Felix SB;Ferrières 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;Järvelin MR;Jukema JW;Kardia SLR;Kee F;Kooner JS;Kooperberg C;Launer LJ;Lind L;Loos RJF;Majumder AAS;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 WH;Smith BH;Soranzo N;Spector TD;Starr JM;Sebert S;Taylor KD;Lakka TA;Timpson NJ;Tobin MD;Understanding Society Scientific Group;van der Harst P;van der Meer P;Ramachandran VS;Verweij N;Virtamo J;Völker U;Weir DR;Zeggini E;Charchar FJ;Million Veteran Program;Wareham NJ;Langenberg C;Tomaszewski M;Butterworth AS;Caulfield MJ;Danesh J;Edwards TL;Holm H;Hung AM;Lindgren CM;Liu C;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
迄今为止，血压（BP）的遗传研究主要分析常见变异（次要等位基因频率，MAF > 0.05）。在一项超过130万参与者的荟萃分析中，我们发现了106个新的BP相关基因组区域和87个罕见的（MAF ≤ 0.01）变异BP关联（P < 5 × 10-8），其中32个位于新的BP相关基因座，55个是已知BP相关区域内的独立BP相关SNV。罕见变异体（44%编码）的平均效应比常见变异体效应大约8倍，表明新的和已知基因座（例如GATA 5、PLCB 3）存在潜在的候选致病基因。BP相关变异体（包括罕见和常见）在胎儿组织中的活性染色质区域富集，可能将胎儿发育与以后生活中的BP调节联系起来。多变量孟德尔随机化提示收缩压和舒张压升高对大动脉卒中可能有相反的影响。我们的研究证明了罕见变异分析在识别候选基因方面的实用性，结果突出了潜在的治疗靶点。
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency, MAF > 0.05). In a meta-analysis of up to >1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (MAF ≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated SNVs within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (e.g. GATA5, 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.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1016/s0140-6736(17)31928-1
发表时间：
2017-11-25
期刊：
Lancet (London, England)
影响因子：
--
作者：
Di Angelantonio E;Thompson SG;Kaptoge S;Moore C;Walker M;Armitage J;Ouwehand WH;Roberts DJ;Danesh J;INTERVAL Trial Group
通讯作者：
INTERVAL Trial Group
使用密集的插图地图发现与与心脏代谢风险相关的遗传基因座的发现和完善。
影响因子：
30.8
作者：
Iotchkova V;Huang J;Morris JA;Jain D;Barbieri C;Walter K;Min JL;Chen L;Astle W;Cocca M;Deelen P;Elding H;Farmaki AE;Franklin CS;Franberg M;Gaunt TR;Hofman A;Jiang T;Kleber ME;Lachance G;Luan J;Malerba G;Matchan A;Mead D;Memari Y;Ntalla I;Panoutsopoulou K;Pazoki R;Perry JRB;Rivadeneira F;Sabater-Lleal M;Sennblad B;Shin SY;Southam L;Traglia M;van Dijk F;van Leeuwen EM;Zaza G;Zhang W;UK10K Consortium;Amin N;Butterworth A;Chambers JC;Dedoussis G;Dehghan A;Franco OH;Franke L;Frontini M;Gambaro G;Gasparini P;Hamsten A;Issacs A;Kooner JS;Kooperberg C;Langenberg C;Marz W;Scott RA;Swertz MA;Toniolo D;Uitterlinden AG;van Duijn CM;Watkins H;Zeggini E;Maurano MT;Timpson NJ;Reiner AP;Auer PL;Soranzo N
通讯作者：
Soranzo N
影响因子：
3.7
作者：
Best KA;Bone DB;Vilas G;Gros R;Hammond JR
通讯作者：
Hammond JR
影响因子：
17.1
作者：
Finan C;Gaulton A;Kruger FA;Lumbers RT;Shah T;Engmann J;Galver L;Kelley R;Karlsson A;Santos R;Overington JP;Hingorani AD;Casas JP
通讯作者：
Casas JP