Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
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在多个祖先的多达570k个个体中，通过基因 - 酒精相互作用鉴定出血压的新型遗传关联。
DOI：
10.1371/journal.pone.0198166
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Levy D
中科院分区：
文献类型：
--
作者：
Feitosa MF;Kraja AT;Chasman DI;Sung YJ;Winkler TW;Ntalla I;Guo X;Franceschini N;Cheng CY;Sim X;Vojinovic D;Marten J;Musani SK;Li C;Bentley AR;Brown MR;Schwander K;Richard MA;Noordam R;Aschard H;Bartz TM;Bielak LF;Dorajoo R;Fisher V;Hartwig FP;Horimoto ARVR;Lohman KK;Manning AK;Rankinen T;Smith AV;Tajuddin SM;Wojczynski MK;Alver M;Boissel M;Cai Q;Campbell A;Chai JF;Chen X;Divers J;Gao C;Goel A;Hagemeijer Y;Harris SE;He M;Hsu FC;Jackson AU;Kähönen M;Kasturiratne A;Komulainen P;Kühnel B;Laguzzi F;Luan J;Matoba N;Nolte IM;Padmanabhan S;Riaz M;Rueedi R;Robino A;Said MA;Scott RA;Sofer T;Stančáková A;Takeuchi F;Tayo BO;van der Most PJ;Varga TV;Vitart V;Wang Y;Ware EB;Warren HR;Weiss S;Wen W;Yanek LR;Zhang W;Zhao JH;Afaq S;Amin N;Amini M;Arking DE;Aung T;Boerwinkle E;Borecki I;Broeckel U;Brown M;Brumat M;Burke GL;Canouil M;Chakravarti A;Charumathi S;Ida Chen YD;Connell JM;Correa A;de Las Fuentes L;de Mutsert R;de Silva HJ;Deng X;Ding J;Duan Q;Eaton CB;Ehret G;Eppinga RN;Evangelou E;Faul JD;Felix SB;Forouhi NG;Forrester T;Franco OH;Friedlander Y;Gandin I;Gao H;Ghanbari M;Gigante B;Gu CC;Gu D;Hagenaars SP;Hallmans G;Harris TB;He J;Heikkinen S;Heng CK;Hirata M;Howard BV;Ikram MA;InterAct Consortium;John U;Katsuya T;Khor CC;Kilpeläinen TO;Koh WP;Krieger JE;Kritchevsky SB;Kubo M;Kuusisto J;Lakka TA;Langefeld CD;Langenberg C;Launer LJ;Lehne B;Lewis CE;Li Y;Lin S;Liu J;Liu J;Loh M;Louie T;Mägi R;McKenzie CA;Meitinger T;Metspalu A;Milaneschi Y;Milani L;Mohlke KL;Momozawa Y;Nalls MA;Nelson CP;Sotoodehnia N;Norris JM;O'Connell JR;Palmer ND;Perls T;Pedersen NL;Peters A;Peyser PA;Poulter N;Raffel LJ;Raitakari OT;Roll K;Rose LM;Rosendaal FR;Rotter JI;Schmidt CO;Schreiner PJ;Schupf N;Scott WR;Sever PS;Shi Y;Sidney S;Sims M;Sitlani CM;Smith JA;Snieder H;Starr JM;Strauch K;Stringham HM;Tan NYQ;Tang H;Taylor KD;Teo YY;Tham YC;Turner ST;Uitterlinden AG;Vollenweider P;Waldenberger M;Wang L;Wang YX;Wei WB;Williams C;Yao J;Yu C;Yuan JM;Zhao W;Zonderman AB;Becker DM;Boehnke M;Bowden DW;Chambers JC;Deary IJ;Esko T;Farrall M;Franks PW;Freedman BI;Froguel P;Gasparini P;Gieger C;Jonas JB;Kamatani Y;Kato N;Kooner JS;Kutalik Z;Laakso M;Laurie CC;Leander K;Lehtimäki T;Study LC;Magnusson PKE;Oldehinkel AJ;Penninx BWJH;Polasek O;Porteous DJ;Rauramaa R;Samani NJ;Scott J;Shu XO;van der Harst P;Wagenknecht LE;Wareham NJ;Watkins H;Weir DR;Wickremasinghe AR;Wu T;Zheng W;Bouchard C;Christensen K;Evans MK;Gudnason V;Horta BL;Kardia SLR;Liu Y;Pereira AC;Psaty BM;Ridker PM;van Dam RM;Gauderman WJ;Zhu X;Mook-Kanamori DO;Fornage M;Rotimi CN;Cupples LA;Kelly TN;Fox ER;Hayward C;van Duijn CM;Tai ES;Wong TY;Kooperberg C;Palmas W;Rice K;Morrison AC;Elliott P;Caulfield MJ;Munroe PB;Rao DC;Province MA;Levy D
大量饮酒是高血压的既定危险因素;饮酒影响血压（BP）调节的机制仍不清楚。我们假设，一个全基因组关联研究占基因酒精消费的相互作用BP可能会发现额外的BP位点，并有助于了解酒精相关的BP调节。我们进行了一个大型的两阶段调查，结合主要的遗传效应和单核苷酸变异（SNV）-酒精消费的相互作用的联合测试。在第一阶段，对多个血统群体的约131，000个个体进行全基因组发现荟萃分析，产生了3，514个SNV（245个基因座），并有暗示性的关联证据（P < 1.0 x 10 - 5）。在第2阶段，这些SNV在多个祖先的10440 K个体中进行独立外部复制测试。我们在欧洲血统和多血统荟萃分析中鉴定并复制了（在Bonferroni校正阈值下）5个新的BP位点（21个基因中的380个SNV）和49个先前报道的BP位点（109个基因中的2，159个SNV）（P < 5.0 x 10−8）。对于非洲血统样本，我们在第1阶段检测到18个潜在的新BP位点（P < 5.0 x 10−8），值得进一步复制。此外，相关荟萃分析确定了8个新的BP位点（11个基因）。这些基因座中的几个基因（例如，PINX 1、GATA 4、BLK、FTO和GABBR 2）与饮酒有关。这些发现为酒精消费在高血压遗传结构中的作用提供了见解。
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10−5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10−8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
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
DOI：
10.1016/j.ecl.2014.02.005
发表时间：
2014-06-01
影响因子：
4.5
作者：
Danzi, Sara;Klein, Irwin
通讯作者：
Klein, Irwin
DOI：
10.1111/j.1530-0277.2010.01156.x
发表时间：
2010-05
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Edenberg HJ;Koller DL;Xuei X;Wetherill L;McClintick JN;Almasy L;Bierut LJ;Bucholz KK;Goate A;Aliev F;Dick D;Hesselbrock V;Hinrichs A;Kramer J;Kuperman S;Nurnberger JI Jr;Rice JP;Schuckit MA;Taylor R;Todd Webb B;Tischfield JA;Porjesz B;Foroud T
通讯作者：
Foroud T
影响因子：
30.8
作者：
Ehret, Georg B.;Ferreira, Teresa;Chasman, Daniel I.;Jackson, Anne U.;Schmidt, Ellen M.;Johnson, Toby;Thorleifsson, Gudmar;Luan, Jian'an;Donnelly, Louise A.;Kanoni, Stavroula;Petersen, Ann -Kristin;Pihurl, Vasyl;Strawbridge, Rona J.;Shungin, Dmitry;Hughes, Maria F.;Meirelles, Osorio;Kaakinen, Marika;Bouatia-Naji, Nabila;Kristiansson, Kati;Shah, Sonia;Kleber, Marcus E.;Guo, Xiuqing;Lyytikainen, Leo-Pekka;Fava, Cristiano;Eriksson, Nidas;Nolte, Ilja M.;Magnusson, Patrik K.;Salfati, Elias L.;Rallidis, Loukianos S.;Theusch, Elizabeth;Smith, Andrew J. P.;Folkersen, Lasse;Witkowska, Kate;Pers, Tune H.;Joehanes, Roby;Kim, Stuart K.;Lataniotis, Lazaros;Jansen, Rick;Johnson, Andrew D.;Warren, Helen;Kim, Young Jin;Zhao, Wei;Wu, Ying;Tayo, Bamidele O.;Bochud, Murielle;Absher, Devin;Adair, Linda S.;Amin, Najaf;Arkingl, Dan E.;Axelsson, Tomas;Baldassarre, Damian;Balkau, Beverley;Bandinelli, Stefania;Barnes, Michael R.;Barroso, Ines;Bevan, Stephen;Bis, Joshua C.;Bjornsdottir, Gyda;Boehnke, Michael;Boerwinkle, Eric;Bonnycastle, Lori L.;Boomsma, Dorret I.;Bornstein, Stefan R.;Brown, Morris J.;Burnier, Michel;Cabrera, Claudia P.;Chambers, John C.;Chang, I-Shou;Cheng, Ching-Yu;Chines, Peter S.;Chung, Ren-Hua;Collins, Francis S.;Connell, John M.;Doring, Angela;Dallongeville, Jean;Danesh, John;de Faire, Ulf;Delgado, Graciela;Dominiczak, Anna F.;Doney, Alex S. F.;Drenos, Fotios;Edkins, Sarah;Eicher, John D.;Elosua, Roberto;Enroth, Stefan;Erdmann, Jeanette;Eriksson, Per;Esko, Tonu;Evangelou, Evangelos;Evans, Alun;Fai, Tove;Farra, Martin;Felixl, Janine F.;Ferrieres, Jean;Ferrucci, Luigi;Fornage, Myriam;Forrester, Terrence;Franceschinil, Nora;Franco, Oscar H.;Franco-Cereceda, Anders;Fraser, Ross M.;Ganesh, Santhi K.;Gao, He;Gertow, Karl;Gianfagna, Francesco;Gigante, Bruna;Giulianini, Franco;Goe, Anuj;Goodall, Alison H.;Goodarzi, Mark;Gorski, Mathias;Grassler, Jurgen;Groves, Christopher J.;Gudnason, Vilmundur;Gyllensten, Ulf;Hallmans, Goran;Hartikainen, Anna-Liisa;Hassinen, Maija;Havulinna, Aki S.;Hayward, Caroline;Hercberg, Serge;Herzig, Karl-Heinz;Hicks, Andrew A.;Hingorani, Aroon D.;Hirschhorn, Joel N.;Hofmanl, Albert;Holmen, Jostein;Holmen, Oddgeir Lingaas;Hottenga, Jouke-Jan;Howard, Phil;Hsiung, Chao A.;Hunt, Steven C.;Ikram, M. Arfan;Illig, Thomas;Iribarren, Carlos;Jensen, Richard A.;Kahonen, Mika;Kang, Hyun Min;Kathiresan, Sekar;Keating, Brendan J.;Khaw, Kay-Tee;Kim, Yun Kyoung;Kim, Eric;Kivimaki, Mika;Klopp, Norman;Kolovou, Genovefa;Komulainen, Pirjo;Kooner, Jaspal S.;Kosova, Gulum;Krauss, Ronald M.;Kuh, Diana;Kutalik, Zoltan;Kuusisto, Johanna;Kvaloy, Kirsti;Lakka, Timo A.;Lee, Nanette R.;Lee, I-Te;Lee, Wen-Jane;Levy, Daniel;Li, Xiaohui;Liang, Kae-Woei;Lin, Honghuang;Lin, Li;Lindstrom, Jaana;Lobbens, Stephane;Mannisto, Satu;Muller, Gabriele;Muller-Nurasyid, Martina;Mach, Francois;Markus, Hugh S.;Marouli, Eirini;McCarthy, Mark I.;McKenzie, Colin A.;Meneton, Pierre;Menni, Cristina;Metspalu, Andres;Mijatovic, Vladan;Moilanen, Leena;Montasser, May E.;Morris, Andrew D.;Morrison, Alanna C.;Mulas, Antonella;Nagaraja, Ramaiah;Narisu, Narisu;Nikus, Kjell;O'Donnell, Christopher J.;O'Reilly, Paul F.;Ong, Ken K.;Paccaud, Fred;Palmer, Cameron D.;Parsa, Afshin;Pedersen, Nancy L.;Penninx, Brenda W.;Perola, Markus;Peters, Annette;Poulter, Neil;Pramstaller, Peter P.;Psaty, Bruce M.;Quertermous, Thomas;Rao, Dabeeru C.;Rasheed, Asif;Rayner, N. William;Renstrom, Frida;Rettig, Rainer;Rice, Kenneth M.;Roberts, Robert;Rose, Lynda M.;Rossouw, Jacques;Samani, Nilesh J.;Sanna, Serena;Saramies, Jouko;Schunkert, Heribert;Sebert, Sylvain;Sheu, Wayne H-H;Shin, Young-Ah;Sim, Xueling;Smit, Johannes H.;Smith, Albert V.;Sosa, Maria X.;Spector, Tim D.;Stancakova, Alena;Stanton, Alice V.;Stirrups, Kathleen E.;Stringham, Heather M.;Sundstrom, Johan;Swift, Amy J.;Syvanen, Ann-Christine;Tai, E-Shyong;Tanaka, Toshiko;Tarasov, Kirill V.;Teumer, Alexander;Thorsteinsdottir, Unnur;Tobin, Martin D.;Tremoli, Elena;Uitterlinden, Andre G.;Uusitupa, Matti;Vaez, Ahmad;Vaidya, Dhananjay;van Duijn, Cornelia M.;van Iperen, Erik P. A.;Vasan, Ramachandran S.;Verwoert, Germaine C.;Virtamo, Jarmo;Vitart, Veronique;Voight, Benjamin F.;Vollenweider, Peter;Wagner, Aline;Wain, Louise V.;Wareham, Nicholas J.;Watldns, Hugh;Weder, Alan B.;Westra, Harm Jan;Wilks, Rainford;Wilsgaard, Tom;Wilson, James F.;Wong, Tien Y.;Yang, Tsun-Po;Yao, Jie;Yengo, Loic;Zhang, Weihua;Zhao, Jing Hua;Zhu, Xiaofeng;Bovet, Pascal;Cooper, Richard S.;Mohlke, Karen L.;Saleheen, Danish;Lee, Jong-Young;Elliott, Paul;Gierman, Hinco J.;Willer, Cristen J.;Franke, Lude;Hovingh, G. Kees;Taylor, Kent D.;Dedoussis, George;Sever, Peter;Wong, Andrew;Lind, Lars;Assimes, Themistocles L.;Njolstad, Inger;Schwarz, Peter E. H.;Langenberg, Claudia;Snieder, Harold;Caulfield, Mark J.;Melander, E.;Laakso, Markku;Saltevo, Juha;Rauramaa, Rainer;Tuomilehto, Jaakko;Ingelsson, Erik;Lehtimaki, Terho;Hveem, Kristian;Palmas, Walter;Marz, Winfried;Kumar, Meena;Salomaa, Veikko;Chen, Yii-Der I.;Rotter, Jerome I.;Froguel, Philippe;Jarvelin, Marjo-Riitta;Lakatta, Edward G.;Kuulasmaa, Kari;Franks, Paul W.;Hamsten, Anders;Wichmann, H-Erich;Palmer, Colin N. A.;Stefansson, Kari;Ridker, Paul M.;Loos, Ruth J. F.;Chalcravarti, Aravinda;Deloukas, Panos;Morris, Andrew P.;Newton-Cheh, Christopher;Munroe, Patricia B.
通讯作者：
Munroe, Patricia B.