Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.
Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.
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多祖先全基因组荟萃分析中的基因-教育程度相互作用识别新的血压位点。
DOI：
10.1038/s41380-020-0719-3
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发表时间：
2021-06
影响因子：
11
通讯作者：
Fornage M
中科院分区：
文献类型：
--
作者：
de Las Fuentes L;Sung YJ;Noordam R;Winkler T;Feitosa MF;Schwander K;Bentley AR;Brown MR;Guo X;Manning A;Chasman DI;Aschard H;Bartz TM;Bielak LF;Campbell A;Cheng CY;Dorajoo R;Hartwig FP;Horimoto ARVR;Li C;Li-Gao R;Liu Y;Marten J;Musani SK;Ntalla I;Rankinen T;Richard M;Sim X;Smith AV;Tajuddin SM;Tayo BO;Vojinovic D;Warren HR;Xuan D;Alver M;Boissel M;Chai JF;Chen X;Christensen K;Divers J;Evangelou E;Gao C;Girotto G;Harris SE;He M;Hsu FC;Kühnel B;Laguzzi F;Li X;Lyytikäinen LP;Nolte IM;Poveda A;Rauramaa R;Riaz M;Rueedi R;Shu XO;Snieder H;Sofer T;Takeuchi F;Verweij N;Ware EB;Weiss S;Yanek LR;Amin N;Arking DE;Arnett DK;Bergmann S;Boerwinkle E;Brody JA;Broeckel U;Brumat M;Burke G;Cabrera CP;Canouil M;Chee ML;Chen YI;Cocca M;Connell J;de Silva HJ;de Vries PS;Eiriksdottir G;Faul JD;Fisher V;Forrester T;Fox EF;Friedlander Y;Gao H;Gigante B;Giulianini F;Gu CC;Gu D;Harris TB;He J;Heikkinen S;Heng CK;Hunt S;Ikram MA;Irvin MR;Kähönen M;Kavousi M;Khor CC;Kilpeläinen TO;Koh WP;Komulainen P;Kraja AT;Krieger JE;Langefeld CD;Li Y;Liang J;Liewald DCM;Liu CT;Liu J;Lohman KK;Mägi R;McKenzie CA;Meitinger T;Metspalu A;Milaneschi Y;Milani L;Mook-Kanamori DO;Nalls MA;Nelson CP;Norris JM;O'Connell J;Ogunniyi A;Padmanabhan S;Palmer ND;Pedersen NL;Perls T;Peters A;Petersmann A;Peyser PA;Polasek O;Porteous DJ;Raffel LJ;Rice TK;Rotter JI;Rudan I;Rueda-Ochoa OL;Sabanayagam C;Salako BL;Schreiner PJ;Shikany JM;Sidney SS;Sims M;Sitlani CM;Smith JA;Starr JM;Strauch K;Swertz MA;Teumer A;Tham YC;Uitterlinden AG;Vaidya D;van der Ende MY;Waldenberger M;Wang L;Wang YX;Wei WB;Weir DR;Wen W;Yao J;Yu B;Yu C;Yuan JM;Zhao W;Zonderman AB;Becker DM;Bowden DW;Deary IJ;Dörr M;Esko T;Freedman BI;Froguel P;Gasparini P;Gieger C;Jonas JB;Kammerer CM;Kato N;Lakka TA;Leander K;Lehtimäki T;Lifelines Cohort Study;Magnusson PKE;Marques-Vidal P;Penninx BWJH;Samani NJ;van der Harst P;Wagenknecht LE;Wu T;Zheng W;Zhu X;Bouchard C;Cooper RS;Correa A;Evans MK;Gudnason V;Hayward C;Horta BL;Kelly TN;Kritchevsky SB;Levy D;Palmas WR;Pereira AC;Province MM;Psaty BM;Ridker PM;Rotimi CN;Tai ES;van Dam RM;van Duijn CM;Wong TY;Rice K;Gauderman WJ;Morrison AC;North KE;Kardia SLR;Caulfield MJ;Elliott P;Munroe PB;Franks PW;Rao DC;Fornage M
教育程度被广泛用作社会经济地位（SES）的替代指标。低 SES 是高血压和高血压 (BP) 的危险因素。为了识别新的 BP 位点，我们使用两个变量“某所大学”（是/否）和“毕业大学”（是/否）进行了多祖先荟萃分析，解释了基因与教育程度的相互作用。使用 1 自由度 (DF) 相互作用项和遗传和相互作用效应的 2DF 联合检验来评估相互作用。对收缩压、舒张压、平均动脉压和脉压进行分析。我们在第一阶段研究 (N=117 438) 中进行了全基因组询问，并在第二阶段研究 (N=293 787) 中对五个祖先群体的有希望的变异进行了跟踪。通过第一阶段和第二阶段的综合荟萃分析，我们在全基因组显着性水平上鉴定了 84 个已知的 BP 位点和 18 个新的 BP 位点 (P<5×10−8)。基于与教育程度相互作用的 1DF 检验确定了两个新基因座，而通过遗传和相互作用效应的 2DF 联合检验确定了其余 16 个基因座。在非洲血统的个体中发现了十个新的基因座。几个新的基因座显示出很强的生物学合理性，因为它们涉及与血压调节有关的生理系统。它们包括涉及中枢神经系统-肾上腺信号轴（ZDHHC17、CADPS、PIK3C2G）、血管结构和功能（GNB3、CDON）以及肾功能（HAS2 和 HAS2-AS1、SLIT3）的基因。总的来说，这些发现表明教育程度或社会经济地位在进一步剖析 BP 遗传结构中发挥着重要作用。
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N=117 438) and follow-up on promising variants in Stage 2 studies (N=293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P<5×10−8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
基因发现和多基因预测，从基因组全基因组协会的教育程度研究中，有110万个人。
影响因子：
30.8
作者：
Lee JJ;Wedow R;Okbay A;Kong E;Maghzian O;Zacher M;Nguyen-Viet TA;Bowers P;Sidorenko J;Karlsson Linnér R;Fontana MA;Kundu T;Lee C;Li H;Li R;Royer R;Timshel PN;Walters RK;Willoughby EA;Yengo L;23andMe Research Team;COGENT (Cognitive Genomics Consortium);Social Science Genetic Association Consortium;Alver M;Bao Y;Clark DW;Day FR;Furlotte NA;Joshi PK;Kemper KE;Kleinman A;Langenberg C;Mägi R;Trampush JW;Verma SS;Wu Y;Lam M;Zhao JH;Zheng Z;Boardman JD;Campbell H;Freese J;Harris KM;Hayward C;Herd P;Kumari M;Lencz T;Luan J;Malhotra AK;Metspalu A;Milani L;Ong KK;Perry JRB;Porteous DJ;Ritchie MD;Smart MC;Smith BH;Tung JY;Wareham NJ;Wilson JF;Beauchamp JP;Conley DC;Esko T;Lehrer SF;Magnusson PKE;Oskarsson S;Pers TH;Robinson MR;Thom K;Watson C;Chabris CF;Meyer MN;Laibson DI;Yang J;Johannesson M;Koellinger PD;Turley P;Visscher PM;Benjamin DJ;Cesarini D
通讯作者：
Cesarini 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. 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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：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M