484 results on '"Ball, SG"'
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2. How I approach hyponatraemia
- Author
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Ball, SG
- Published
- 2013
- Full Text
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3. The prognostic significance of a history of systemic hypertension in patients randomised to either placebo or ramipril following acute myocardial infarction: evidence from the AIRE study
- Author
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Spargias, KS, Ball, SG, and Hall, AS
- Published
- 1999
- Full Text
- View/download PDF
4. ACE INHIBITION IN THE ELDERLY AFTER ACUTE MYOCARDIAL INFARCTION. INSIGHTS FROM THE AIRE STUDY
- Author
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Spargias, KS, Hall, AS, and Ball, SG
- Published
- 1998
5. A state of reversible compensated ventricular dysfunction precedes pathological remodelling in response to cardiomyocyte-specific activity of angiotensin II type-1 receptor in mice
- Author
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Frentzou, GA, Drinkhill, MJ, Turner, NA, Ball, SG, and Ainscough, JFX
- Subjects
Cardiac hypertrophy ,Dysfunction ,lcsh:R ,Renin angiotensin system ,Conditional transgenic mouse ,Remodelling ,lcsh:Pathology ,lcsh:Medicine ,Fibrosis ,lcsh:RB1-214 - Abstract
Cardiac dysfunction is commonly associated with high-blood-pressure-induced cardiomyocyte hypertrophy, in response to aberrant renin-angiotensin system (RAS) activity. Ensuing pathological remodelling promotes cardiomyocyte death and cardiac fibroblast activation, leading to cardiac fibrosis. The initiating cellular mechanisms that underlie this progressive disease are poorly understood. We previously reported a conditional mouse model in which a human angiotensin II type-I receptor transgene (HART) was expressed in differentiated cardiomyocytes after they had fully matured, but not during development. Twelve-month-old HART mice exhibited ventricular dysfunction and cardiomyocyte hypertrophy with interstitial fibrosis following full receptor stimulation, without affecting blood pressure. Here, we show that chronic HART activity in young adult mice causes ventricular dysfunction without hypertrophy, fibrosis or cardiomyocyte death. Dysfunction correlated with reduced expression of pro-hypertrophy markers and increased expression of pro-angiogenic markers in the cardiomyocytes experiencing increased receptor load. This stimulates responsive changes in closely associated non-myocyte cells, including the downregulation of pro-angiogenic genes, a dampened inflammatory response and upregulation of Tgfβ. Importantly, this state of compensated dysfunction was reversible. Furthermore, increased stimulation of the receptors on the cardiomyocytes caused a switch in the secondary response from the non-myocyte cells. Progressive cardiac remodelling was stimulated through hypertrophy and death of individual cardiomyocytes, with infiltration, proliferation and activation of fibroblast and inflammatory cells, leading to increased angiogenic and inflammatory signalling. Together, these data demonstrate that a state of pre-hypertrophic compensated dysfunction can exist in affected individuals before common markers of heart disease are detectable. The data also suggest that there is an initial response from the housekeeping cells of the heart to signals emanating from distressed neighbouring cardiomyocytes to suppress those changes most commonly associated with progressive heart disease. We suggest that the reversible nature of this state of compensated dysfunction presents an ideal window of opportunity for personalised therapeutic intervention.
- Published
- 2015
6. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
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Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcus, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Maris, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pirastu, Nicola, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, McArdle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Toomas, Keis, Aime, Tammesoo, Mari-Liis, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Anders, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, James, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thomas, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Gasparini, Paolo, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andres, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willems, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van Duijn, Cornelia M. McEniery CM, Wilkinson IB, Cockcroft JR, O'Shaughnessy KM, Newhouse SJ, Yasmin, Smith AV, Eiriksdottir G, Launer LJ, Sigurdsson S, Aspelund T, Gudnason V, De Bacquer D, Rietzschel ER, De Backer GG, Van Bortel L, De Buyzere ML, Segers P, Bekaert S, Gillebert TC, De Meyer T, Ferrucci L, Tanaka T, Johnson AD, Levy D, Benjamin EJ, Mitchell GF, Vita JA, Larson MG, Hamburg NM, Vasan RS, Isaacs A, Schut AF, Oostra BA, van Duijn CM, van Rijn MJ, Sie MP, Newman AB, Herrington DM, Andrews JS, Ding J, Sutton-Tyrrell KC, Harris TB, Howard TD, Liu Y, Parsa A, Shuldiner AR, McArdle PF, Gibson Q, Post WS, Dehghan A, Hofman A, Uitterlinden AG, Sijbrands EJ, Rivadeneira F, Mattace-Raso FU, Verwoert GC, Witteman JC, Scuteri A, Lakatta EG, Jewell E, Abecasis GR, Tarasov KV, Uda M, Najjar SS, Sanna S, Attwood T, Belz S, Braund P, Cambien F, Cooper J, Crisp-Hihn A, Deloukas P, Foad N, Eardman J, Goodall AH, Gracey J, Gray E, Gulde S, Gwilliams R, Heimerl S, Hengstenberg C, Jolley J, Krishnan U, Linsel-Nitschke P, Lloyd-Jones H, Lugauer I, Lundmark P, Maouche S, Moore JS, Muir D, Murray E, Nelson CP, Neudert J, Niblett D, O'Leary K, Ouwehand WH, Pollard H, Rankin A, Rice CM, Sager H, Samani NJ, Sambrook J, Schmitz G, Scholz M, Schroeder L, Schunkert H, Syvannen AC, Wallace C, Kathiresan S, Reilly MP, Erdmann J, Assimes TL, Boerwinkle E, Hall A, König IR, Laaksonen R, McPherson R, Thompson JR, Thorsteinsdottir U, Ziegler A, Absher D, Chen L, Cupples LA, Halperin E, Li M, Musunuru K, Preuss M, Schillert A, Thorleifsson G, Voight BF, Wells GA, Assime TL, Holm H, Roberts R, Stewart AF, Fortmann S, Go A, Hlatky M, Iribarren C, Knowles J, Myers R, Quertermous T, Sidney S, Risch N, Tang H, Blankenberg S, Zeller T, Wild P, Schnabel R, Sinning C, Lackner K, Tiret L, Nicaud V, Bickel C, Rupprecht HJ, Perret C, Proust C, Münzel T, Barbalic M, Bis J, Chen IY, Cupples L, Demissie-Banjaw S, Folsom A, Glazer N, Harris T, Heckbert S, Lumley T, Marciante K, Morrison A, O' Donnell CJ, Psaty BM, Rice K, Rotter JI, Siscovick DS, Smith N, Smith A, Taylor KD, van Duijn C, Volcik K, Whitteman J, Ramachandran V, Uitterlinden A, Gretarsdottir S, Gulcher JR, Kong A, Stefansson K, Thorgeirsson G, Andersen K, Fischer M, Grosshennig A, Lieb W, Stark K, Schreiber S, Wichmann HE, Aherrahrou Z, Bruse P, Doering A, Illig T, Klopp N, Loley C, Medack A, Meisinger C, Meitinger T, Nahrstedt J, Peters A, Wagner AK, Willenborg C, Böhm BO, Dobnig H, Grammer TB, Hoffmann MM, Kleber M, März W, Meinitzer A, Winkelmann BR, Pilz S, Renner W, Scharnagl H, Stojakovic T, Tomaschitz A, Winkler K, Guiducci C, Burtt N, Gabriel SB, O'Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, Dandona S, Jarinova O, Qu L, Wilensky R, Matthai W, Hakonarson HH, Devaney J, Burnett MS, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Knouff CW, Waterworth DM, Walker MC, Mooser V, Epstein SE, Rader DJ, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall AS, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Yang YA, Stricker BH, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Willerson JT, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Gao X, Yang Q, O'Connell JR, Schmidt H, Ketkar S, Hwang SJ, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria F, Metter J, de Boer IH, Siscovick D, Zillikens MC, Feitosa M, Province M, de Andrade M, Turner ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Coresh J, Schmidt R, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Felix SB, Watzinger N, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Reffelmann T, Redfield MM, Werdan K, Arnett DK, Blettner M, Friedrich N, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic N, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Vollenweider P, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Lightstone L, Scott J, Navis G, Elliott P, Kooner JS., Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), University of Leicester, Department of Genetics [Leicester], Erasmus University Rotterdam, Netherlands Genomics Initiative, Department of Epidemiology and Biostatistics, School of Public Health, Zahedan University of Medical Sciences, Washington University in Saint Louis (WUSTL), Queen Mary University of London (QMUL), National Heart, Lung and Blood Institute, Partenaires INRAE, Centre Hospitalier Universitaire Vaudois (CHUV), Université de Lausanne = University of Lausanne (UNIL), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Leiden University Medical Center (LUMC), Universiteit Leiden, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Department of Epidemiology, The Netherlands Cancer Institute, Department of Mathematics, Boston University [Boston] (BU), GlaxoSmithKline, Division of Community Health Sciences, St. George's, University of South Florida [Tampa] (USF), Universität Greifswald - University of Greifswald, University of Washington [Seattle], University of Tartu, Institute of Molecular and Cell Biology, Medical Research Council, Institut de Génomique, Centre National de Génotypage, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University Medical Center Groningen, Department of Genetics, University Medical Center Groningen [Groningen] (UMCG), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Massachusetts General Hospital [Boston], Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Università degli studi di Trieste = University of Trieste, Universität zu Lübeck = University of Lübeck [Lübeck], Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, The University of Western Australia (UWA), Department of Twin Research and Genetic Epidemiology, King's College London, London, University of Oxford, Medical University Graz, National Institute on Aging, Centre for population Health Sciences, University of Edinburgh, Uppsala University, Vrije Universiteit Amsterdam [Amsterdam] (VU), Western General Hospital, Harvard Medical School [Boston] (HMS), Brigham and Women's Hospital [Boston], University of Michigan System, University of Groningen, Ealing Hospital, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Medical Genetics Institute, Cedars-Sinai Medical Center, University of Tampere, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Split, The University of Texas Health Science Center at Houston (UTHealth), Johns Hopkins University (JHU), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Swiss Institute of Bioinformatics [Lausanne] (SIB), Finnish Institute of Occupational Health, National Institute of Health and Welfare, University of Oulu, Lapland Central Hospital, University of Bristol [Bristol], Institute for Community Medicine, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), US National Institutes of Health, National Heart, Lung, and Blood Institute, European, Epidemiology, Internal Medicine, Public Health, Clinical Genetics, Université de Lausanne (UNIL), LeidenUniversity Medical Centre, University of Iceland, Università degli studi di Trieste, Universität zu Lübeck [Lübeck], University of Western Australia, University of Oxford [Oxford], VU University Amsterdam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Human genetics, Psychiatry, EMGO - Mental health, NCA - Anxiety & Depression, Epidemiology and Data Science, Medical Research Council (MRC), Louise V., Wain, Germaine C., Verwoert, Paul F., O'Reilly, Gang, Shi, Toby, Johnson, Andrew D., Johnson, Murielle, Bochud, Kenneth M., Rice, Peter, Henneman, Albert V., Smith, Georg B., Ehret, Najaf, Amin, Martin G., Larson, Vincent, Mooser, David, Hadley, Marcus, Dörr, Joshua C., Bi, Thor, Aspelund, Tõnu, Esko, A. Cecile J. W., Janssen, Jing Hua, Zhao, Simon, Heath, Maris, Laan, Jingyuan, Fu, Giorgio, Pisti, Jian'An, Luan, Pankaj, Arora, Gavin, Luca, Pirastu, Nicola, Irene, Pichler, Anne U., Jackson, Rebecca J., Webster, Feng, Zhang, John F., Peden, Helena, Schmidt, Toshiko, Tanaka, Harry, Campbell, Wilmar, Igl, Yuri, Milaneschi, Jouke Jan, Hottenga, Veronique, Vitart, Daniel I., Chasman, Stella, Trompet, Jennifer L., Bragg Gresham, Behrooz Z., Alizadeh, John C., Chamber, Xiuqing, Guo, Terho, Lehtimäki, Brigitte, Kühnel, Lorna M., Lopez, Ozren, Polašek, Mladen, Boban, Christopher P., Nelson, Alanna C., Morrison, Vasyl, Pihur, Santhi K., Ganesh, Albert, Hofman, Suman, Kundu, Francesco U. S., Mattace Raso, Fernando, Rivadeneira, Eric J. G., Sijbrand, Andre G., Uitterlinden, Shih Jen, Hwang, Ramachandran S., Vasan, Thomas J., Wang, Sven, Bergmann, Peter, Vollenweider, Gérard, Waeber, Jaana, Laitinen, Anneli, Pouta, Paavo, Zitting, Wendy L., Mcardle, Heyo K., Kroemer, Uwe, Völker, Henry, Völzke, Nicole L., Glazer, Kent D., Taylor, Tamara B., Harri, Helene, Alavere, Toomas, Haller, Aime, Kei, Mari Liis, Tammesoo, Yurii, Aulchenko, Inês, Barroso, Kay Tee, Khaw, Pilar, Galan, Serge, Hercberg, Mark, Lathrop, Susana, Eyheramendy, Elin, Org, Siim, Sõber, Xiaowen, Lu, Ilja M., Nolte, Brenda W., Penninx, Tanguy, Corre, Corrado, Masciullo, Cinzia, Sala, Leif, Groop, Benjamin F., Voight, Olle, Melander, Christopher J., O'Donnell, Veikko, Salomaa, D'Adamo, ADAMO PIO, Antonella, Fabretto, Flavio, Faletra, Sheila, Ulivi, Fabiola Del Greco, M, Maurizio, Facheri, Francis S., Collin, Richard N., Bergman, John P., Beilby, Joseph, Hung, A., William Musk, Massimo, Mangino, So Youn, Shin, Nicole, Soranzo, Hugh, Watkin, Anuj, Goel, Anders, Hamsten, Pierre, Gider, Marisa, Loitfelder, Marion, Zeginigg, Dena, Hernandez, Samer S., Najjar, Pau, Navarro, Sarah H., Wild, Anna Maria, Corsi, Andrew, Singleton, Eco J. C., de Geu, Gonneke, Willemsen, Alex N., Parker, Lynda M., Rose, Brendan, Buckley, David, Stott, Marco, Orru, Manuela, Uda, Melanie M., van der Klauw, Weihua, Zhang, Xinzhong, Li, James, Scott, Yii Der Ida, Chen, Gregory L., Burke, Mika, Kähönen, Jorma, Viikari, Angela, Döring, Thomas, Meitinger, Gail, Davie, John M., Starr, Valur, Emilsson, Andrew, Plump, Jan H., Lindeman, Peter A. C., 't Hoen, Inke R., König, Janine F., Felix, Robert, Clarke, Jemma C., Hopewell, Halit, Ongen, Monique, Breteler, Stéphanie, Debette, Anita L., Destefano, Myriam, Fornage, Gary F., Mitchell, Nicholas L., Smith, Hilma, Holm, Kari, Stefansson, Gudmar, Thorleifsson, Unnur, Thorsteinsdottir, Nilesh J., Samani, Michael, Preu, Igor, Rudan, Caroline, Hayward, Ian J., Deary, H., Erich Wichmann, Olli T., Raitakari, Walter, Palma, Jaspal S., Kooner, Ronald P., Stolk, J., Wouter Jukema, Alan F., Wright, Dorret I., Boomsma, Stefania, Bandinelli, Ulf B., Gyllensten, James F., Wilson, Luigi, Ferrucci, Reinhold, Schmidt, Martin, Farrall, Tim D., Spector, Lyle J., Palmer, Jaakko, Tuomilehto, Arne, Pfeufer, Gasparini, Paolo, David, Siscovick, David, Altshuler, Ruth J. F., Loo, Daniela, Toniolo, Harold, Snieder, Christian, Gieger, Pierre, Meneton, Nicholas J., Wareham, Ben A., Oostra, Andres, Metspalu, Lenore, Launer, Rainer, Rettig, David P., Strachan, Jacques S., Beckmann, Jacqueline C. M., Witteman, Jeanette, Erdmann, Ko Willems van, Dijk, Eric, Boerwinkle, Michael, Boehnke, Paul M., Ridker, Marjo Riitta, Jarvelin, Aravinda, Chakravarti, Goncalo R., Abecasi, Vilmundur, Gudnason, Christopher Newton, Cheh, Daniel, Levy, Patricia B., Munroe, Bruce M., Psaty, Mark J., Caulfield, Dabeeru C., Rao, Martin D., Tobin, Paul, Elliott, Cornelia M., van Duijn, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcu, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Mari, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, Mcardle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Tooma, Keis, Aime, Tammesoo, Mari-Lii, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Ander, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. 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Netherlands Twin Register (NTR) ,Linkage disequilibrium ,pulse pressure ,mean arterial pressure ,genome-wide ,[SDV]Life Sciences [q-bio] ,Genome-wide association study ,BLOOD-PRESSURE ,Blood Pressure ,030204 cardiovascular system & hematology ,Linkage Disequilibrium ,0302 clinical medicine ,RELEVANCE ,CardioGram ,Medicine and Health Sciences ,Genetics & Heredity ,ddc:616 ,Genetics ,0303 health sciences ,Genome-wide association ,11 Medical And Health Sciences ,Arteries ,ADRENERGIC-RECEPTOR TRAFFICKING ,Pulse pressure ,EchoGen consortium ,Hypertension ,HEART-FAILURE ,arterial pressure ,Case-Control Studie ,Life Sciences & Biomedicine ,Human ,circulatory and respiratory physiology ,medicine.medical_specialty ,Mean arterial pressure ,Arterie ,AortaGen Consortium ,Cardiogenics consortium ,Locus (genetics) ,Biology ,Polymorphism, Single Nucleotide ,Article ,Follow-Up Studie ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,METAANALYSIS ,030304 developmental biology ,Genetic association ,Science & Technology ,HYPERTENSION ,MORTALITY ,Case-control study ,CARDIOVASCULAR-DISEASE RISK ,06 Biological Sciences ,GENE ,MICE ,Endocrinology ,Blood pressure ,CKDGen consortium ,Genetic Loci ,Case-Control Studies ,KidneyGen consortium ,CHARGE Consortium Heart Failure Working Group ,LifeLines Cohort Study ,Developmental Biology ,Follow-Up Studies ,Genome-Wide Association Study - Abstract
Les affiliations des 100 premiers auteurs sont renseignées dans la notice. Les affiliations des autres auteurs sont disponibles à la fin de la publication.; International audience; Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
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- 2016
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7. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
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M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang H, Knowles J, Hlatky M, Fortmann S, Assimes TL, Quertermous T, Go A, Iribarren C, Absher D, Risch N, Meyers R, Sidney S, Ziegler A, Schillert A, Bickel C, Sinning C, Rupprecht HJ, Lackner K, Wild P, Schnabel R, Blankenberg S, Zeller T, Münzel T, Perret C, Cambien F, Tiret L, Nicaud V, Proust C, Dehghan A, Hofman A, Uitterlinden A, van Duijn C, Levy D, Whitteman J, Cupples LA, Demissie-Banjaw S, Ramachandran V, Smith A, Gudnason V, Boerwinkle E, Folsom A, Morrison A, Psaty BM, Chen IY, Rotter JI, Bis J, Volcik K, Rice K, Taylor KD, Marciante K, Smith N, Glazer N, Heckbert S, Harris T, Lumley T, Kong A, Thorleifsson G, Thorgeirsson G, Holm H, Gulcher JR, Stefansson K, Andersen K, Gretarsdottir S, Thorsteinsdottir U, Preuss M, Schreiber S, Meitinger T, König IR, Lieb W, Hengstenberg C, Schunkert H, Erdmann J, Fisher M, Grosshennig A, Medack A, Stark K, Linsel-Nitschke P, Bruse P, Aherrahrou Z, Peters A, Loley C, Willenborg C, Nahrstedt J, Freyer J, Gulde S, Doering A, Meisinger C, Wichmann HE, Klopp N, Illig T, Meinitzer A, Tomaschitz A, Halperin E, Dobnig H, Scharnagl H, Kleber M, Laaksonen R, Pilz S, Grammer TB, Stojakovic T, Renner W, März W, Böhm BO, Winkelmann BR, Winkler K, Hoffmann M, O'Donnell CJ, Voight BF, Altshuler D, Siscovick DS, Musunuru K, Peltonen L, Barbalic M, Melander O, Elosua R, Kathiresan S, Schwartz SM, Salomaa V, Guiducci C, Burtt N, Gabriel SB, Stewart AF, Wells GA, Chen L, Jarinova O, Roberts R, McPherson R, Dandona S, Pichard AD, Rader DJ, Devaney J, Lindsay JM, Kent KM, Qu L, Satler L, Burnett MS, Li M, Reilly MP, Wilensky R, Waksman R, Epstein S, Mattha W, Knouf CW, Waterworth DM, Hakonarson HH, Walker M, Mooser V, Hall AS, Balmforth AJ, Wright BJ, Nelson C, Thompson JR, Samani NJ, Braund PS, Ball SG, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Rivadeneira F, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Wang YA, Stricker B, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Uitterlinden AG, Willerson JT, van Duijn CM, Witteman JC, Vasan RS, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Parsa A, Gao X, Yang Q, Smith AV, O'Connell JR, Schmidt H, Tanaka T, Isaacs A, Ketkar S, Hwang SJ, Johnson A, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Aspelund T, Eiriksdottir G, Launer LJ, Harris TB, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria, Francesco, Metter J, de Boer J, Siscovick D, Zillikens MC, Oostra BA, Feitosa M, Province M, de Andrade M, Turne ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Liu Y, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Shuldiner AR, Coresh J, Schmidt R, Ferrucci L, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Vasan R, Felix SB, Watzinger N, Larson MG, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Stricker BH, Reffelmann T, Redfield MM, Werdan K, Mitchell GF, Arnett D, Blettner M, Friedrich N, Benjamin EJ, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic T, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Sanna S, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Uda M, Vollenweider P, Wallace C, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Abecasis GR, Lightstone L, Scott J, Navis G, Elliot P, Kooner JS., AII - Amsterdam institute for Infection and Immunity, Nephrology, Epidemiologie, RS: CARIM School for Cardiovascular Diseases, Epidemiology, Medical Microbiology & Infectious Diseases, Radiology & Nuclear Medicine, Cardiology, Internal Medicine, Clinical Genetics, Erasmus MC other, Obstetrics & Gynecology, International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Zhao, Jing Hua [0000-0003-4930-3582], Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Khaw, Kay-Tee [0000-0002-8802-2903], Danesh, John [0000-0003-1158-6791], Soranzo, Nicole [0000-0003-1095-3852], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Clinical Pharmacology and The Genome Centre, Queen Mary University of London (QMUL), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Center for Human Genetic Research, Massachusetts General Hospital [Boston], Program in Medical and Population Genetics, Harvard University-Massachusetts Institute of Technology (MIT), 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, Abba, 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, Sjögren, 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, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., 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, Hunter Young, J., Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthia, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johanne, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inê, 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, Marku, 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, Margu, 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, Thoma, Wichmann, H. -Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, Jame, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, O'Donnell, Christopher J., Schwartz, Stephen M., Arfan Ikram, M., Longstreth Jr., W. T., 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, Ander, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., 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., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcu, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Pano, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Jano, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charle, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Mari, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. 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., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang, H, Knowles, J, Hlatky, M, Fortmann, S, Assimes, Tl, Quertermous, T, Go, A, Iribarren, C, Absher, D, Risch, N, Meyers, R, Sidney, S, Ziegler, A, Schillert, A, Bickel, C, Sinning, C, Rupprecht, Hj, Lackner, K, Wild, P, Schnabel, R, Blankenberg, S, Zeller, T, Münzel, T, Perret, C, Cambien, F, Tiret, L, Nicaud, V, Proust, C, Dehghan, A, Hofman, A, Uitterlinden, A, van Duijn, C, Levy, D, Whitteman, J, Cupples, La, Demissie-Banjaw, S, Ramachandran, V, Smith, A, Gudnason, V, Boerwinkle, E, Folsom, A, Morrison, A, Psaty, Bm, Chen, Iy, Rotter, Ji, Bis, J, Volcik, K, Rice, K, Taylor, Kd, Marciante, K, Smith, N, Glazer, N, Heckbert, S, Harris, T, Lumley, T, Kong, A, Thorleifsson, G, Thorgeirsson, G, Holm, H, Gulcher, Jr, Stefansson, K, Andersen, K, Gretarsdottir, S, Thorsteinsdottir, U, Preuss, M, Schreiber, S, Meitinger, T, König, Ir, Lieb, W, Hengstenberg, C, Schunkert, H, Erdmann, J, Fisher, M, Grosshennig, A, Medack, A, Stark, K, Linsel-Nitschke, P, Bruse, P, Aherrahrou, Z, Peters, A, Loley, C, Willenborg, C, Nahrstedt, J, Freyer, J, Gulde, S, Doering, A, Meisinger, C, Wichmann, He, Klopp, N, Illig, T, Meinitzer, A, Tomaschitz, A, Halperin, E, Dobnig, H, Scharnagl, H, Kleber, M, Laaksonen, R, Pilz, S, Grammer, Tb, Stojakovic, T, Renner, W, März, W, Böhm, Bo, Winkelmann, Br, Winkler, K, Hoffmann, M, O'Donnell, Cj, Voight, Bf, Altshuler, D, Siscovick, D, Musunuru, K, Peltonen, L, Barbalic, M, Melander, O, Elosua, R, Kathiresan, S, Schwartz, Sm, Salomaa, V, Guiducci, C, Burtt, N, Gabriel, Sb, Stewart, Af, Wells, Ga, Chen, L, Jarinova, O, Roberts, R, Mcpherson, R, Dandona, S, Pichard, Ad, Rader, Dj, Devaney, J, Lindsay, Jm, Kent, Km, Qu, L, 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H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliot, P, and Kooner, Js.
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novel loci ,Kidney Disease ,Polymorphism, Single Nucleotide/*genetics ,[SDV]Life Sciences [q-bio] ,left ventricular wall thickness ,LOCI ,Genome-wide association study ,Blood Pressure ,Disease ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Coronary artery disease ,0302 clinical medicine ,RELEVANCE ,Africa/ethnology ,Cardiovascular Disease ,genetics ,Kidney Diseases/genetics ,Stroke ,genome wide association study ,POPULATION ,ta118 ,Blood pressure ,hypertension ,stroke ,coronary artery disease ,ddc:616 ,0303 health sciences ,education.field_of_study ,Asia/ethnology ,Multidisciplinary ,Coronary Artery Disease/genetics ,COMMON VARIANTS ,Genetic Predisposition to Disease/*genetics ,3. Good health ,Europe ,Cardiovascular Diseases ,Hypertension ,Cardiology ,Kidney Diseases ,HEALTH ,Human ,medicine.medical_specialty ,Asia ,Population ,Renal function ,Polymorphism, Single Nucleotide ,Europe/ethnology ,Article ,CLONING ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Stroke/genetics ,Internal medicine ,medicine ,Humans ,Cardiovascular Diseases/*genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,education ,METAANALYSIS ,030304 developmental biology ,RECEPTOR ,genes ,blood pressure ,cardiovascular disease risk ,medicine.disease ,Africa ,Blood Pressure/*genetics/physiology ,Hypertension/genetics ,Kidney disease ,Genome-Wide Association Study - Abstract
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. ispartof: Nature vol:478 issue:7367 pages:103-109 ispartof: location:England status: published
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- 2011
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8. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure
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Julian, DG, Moss, AJ, Murray, GD, Poole-Wilson, PA, Simoons, ML, Ball, SG, Bender, N, Cleland, JGF, Clement, DL, Commerford, PJ, Volta, S Dalla, Delagardelle, C, Erhardt, L, Fennell, W, Hall, AS, Hopf, R, Jagerholm, S, Jolly, M, Klein, W, Murray, GD, Niemeyer, MG, Rasmussen, S, Riccitelli, MA, Richardson, L, Stonier, PD, Vogelin, H-P, and Winter, C
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- 1993
9. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
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Burton, PR, Clayton, DG, Cardon, LR, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Samani, NJ, Todd, JA, Donnelly, P, Barrett, JC, Davison, D, Easton, D, Evans, DM, Leung, HT, Marchini, JL, Morris, AP, Spencer, CC, Tobin, MD, Attwood, AP, Boorman, JP, Cant, B, Everson, U, Hussey, JM, Jolley, JD, Knight, AS, Koch, K, Meech, E, Nutland, S, Prowse, CV, Stevens, HE, Taylor, NC, Walters, GR, Walker, NM, Watkins, NA, Winzer, T, Jones, RW, McArdle, WL, Ring, SM, Strachan, DP, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon-Smith, K, Jones, L, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskivina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGuffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, TD, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Thompson, JR, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Forbes, A, Lewis, CM, Onnie, CM, Prescott, NJ, Sanderson, J, Matthew, CG, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Webster, J, Brown, MJ, Lathrop, MG, Connell, J, Dominiczak, A, Marcano, CA, Burke, B, Dobson, R, Gungadoo, J, Lee, KL, Munroe, PB, Newhouse, SJ, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hilder, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DP, Thomson, W, Worthington, J, Dunger, DB, Widmer, B, Frayling, TM, Freathy, RM, Lango, H, Perry, JR, Shields, BM, Weedon, MN, Hattersley, AT, Hitman, GA, Walker, M, Elliott, KS, Groves, CJ, Lindgren, CM, Rayner, NW, Timpson, NJ, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, AV, Bradbury, LA, Farrar, C, Pointon, JJ, Wordsworth, P, Brown, MA, Franklyn, JA, Heward, JM, Simmonds, MJ, Gough, SC, Seal, S, Stratton, MR, Rahman, N, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Conway, D, Jallow, M, Rockett, KA, Bumpstead, SJ, Chaney, A, Downes, K, Ghori, MJ, Gwilliam, R, Hunt, SE, Inouye, M, Keniry, A, King, E, McGinnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdo'ttir, IB, Howie, BN, Su, Z, Teo, YY, Vukcevic, D, Bentley, D, Mitchell, SL, Newby, PR, Brand, OJ, Carr-Smith, J, Pearce, SH, Reveille, JD, Zhou, X, Sims, AM, Dowling, A, Taylor, J, Doan, T, Davis, JC, Savage, L, Ward, MM, Learch, TL, Weisman, MH, and Brown, M
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Linkage disequilibrium ,Multiple Sclerosis ,Genotype ,Population ,Single-nucleotide polymorphism ,Genome-wide association study ,Autoimmunity ,Breast Neoplasms ,Biology ,medicine.disease_cause ,Aminopeptidases ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Article ,Minor Histocompatibility Antigens ,Genetics ,medicine ,Humans ,Spondylitis, Ankylosing ,Receptors, Immunologic ,education ,Genetic association ,education.field_of_study ,Ankylosing spondylitis ,Thyroiditis, Autoimmune ,Chromosome Mapping ,Receptors, Interleukin ,medicine.disease ,Endoplasmic reticulum aminopeptidase 2 ,Genetics, Population ,Haplotypes ,Case-Control Studies ,Immunology ,North America - Abstract
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
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- 2016
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10. Large-scale gene-centric analysis identifies novel variants for coronary artery disease
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Butterworth, As, Braund, Ps, Farrall, M, Hardwick, Rj, Saleheen, D, Peden, Jf, Soranzo, N, Chambers, Jc, Sivapalaratnam, S, Kleber, Me, Keating, B, Qasim, A, Klopp, N, Erdmann, J, Assimes, Tl, Ball, Sg, Balmforth, Aj, Barnes, Ta, Basart, H, Baumert, J, Bezzina, Cr, Boerwinkle, E, Boehm, Bo, Brocheton, J, Bugert, P, Cambien, F, Clarke, R, Codd, V, Collins, R, Couper, D, Cupples, La, de Jong JS, Diemert, P, Ejebe, K, Elbers, Cc, Elliott, P, Fornage, M, Franzosi, Mg, Frossard, P, Garner, S, Goel, A, Goodall, Ah, Hengstenberg, C, Hunt, Se, Kastelein, Jj, Klungel, Oh, Klüter, H, Koch, K, König, Ir, Kooner, As, Laaksonen, R, Lathrop, M, Li, M, Liu, K, Mcpherson, R, Musameh, Md, Musani, S, Nelson, Cp, O'Donnell, Cj, Ongen, H, Papanicolaou, G, Peters, A, Peters, Bj, Potter, S, Psaty, Bm, Qu, L, Rader, Dj, Rasheed, A, Rice, C, Scott, J, Seedorf, U, Sehmi, Js, Sotoodehnia, N, Stark, K, Stephens, J, van der Schoot CE, van der Schouw YT, Thorsteinsdottir, U, Tomaszewski, M, van der Harst, P, Vasan, Rs, Wilde, Aa, Willenborg, C, Winkelmann, Br, Zaidi, M, Zhang, W, Ziegler, A, de Bakker PI, Koenig, W, Mätz, W, Trip, Md, Reilly, Mp, Kathiresan, S, Schunkert, H, Hamsten, A, Hall, As, Kooner, Js, Thompson, Sg, Thompson, Jr, Deloukas, P, Ouwehand, Wh, Watkins, H, Danesh, J, Samani, Nj, Barnes, T, Rafelt, S, Bruinsma, N, Dekker, Lr, Henriques, Jp, Koch, Kt, de Winter RJ, Alings, M, Allaart, Cf, Gorgels, Ap, Verheugt, Fw, Mueller, M, Meisinger, C, Derohannessian, S, Mehta, Nn, Ferguson, J, Hakonarson, H, Matthai, W, Wilensky, R, Hopewell, Jc, Parish, S, Linksted, P, Notman, J, Gonzalez, H, Young, A, Ostley, T, Munday, A, Goodwin, N, Verdon, V, Shah, S, Cobb, L, Edwards, C, Mathews, C, Gunter, R, Benham, J, Davies, C, Cobb, M, Crowther, J, Richards, A, Silver, M, Tochlin, S, Mozley, S, Clark, S, Radley, M, Kourellias, K, Silveira, A, Söderholm, B, Olsson, P, Barlera, S, Tognoni, G, Rust, S, Assmann, G, Heath, S, Zelenika, D, Gut, I, Green, F, Peden, J, Aly, A, Anner, K, Björklund, K, Blomgren, G, Cederschiöld, B, Danell Toverud, K, Eriksson, P, Grundstedt, U, Heinonen, M, Hellénius, Ml, van't Hooft, F, Husman, K, Lagercrantz, J, Larsson, A, Larsson, M, Mossfeldt, M, Mälarstig, A, Olsson, G, Sabater Lleal, M, Sennblad, B, Strawbridge, R, Öhrvik, J, Zaman, Ks, Mallick, Nh, Azhar, M, Samad, A, Ishaq, M, Shah, N, Samuel, M, Reilly, M, Holm, H, Preuss, M, Stewart, Af, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, S, Andersen, K, Anderson, Jl, Ardissino, D, Becker, Lc, Becker, Dm, Berger, K, Bis, Jc, Boekholdt, Sm, Brown, Mj, Burnett, Ms, Buysschaert, I, Carlquist, Jf, Chen, L, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, J, Do, R, Doering, A, El Mokhtari NE, Ellis, Sg, Elosua, R, Engert, Jc, Epstein, S, de Faire, U, Fischer, M, Folsom, Ar, Freyer, J, Gigante, B, Girelli, D, Gretarsdottir, S, Gudnason, V, Gulcher, Jr, Tennstedt, S, Halperin, E, Hammond, N, Hazen, Sl, Hofman, A, Horne, Bd, Illig, T, Iribarren, C, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kaplan, Lm, Khaw, Kt, Knowles, Jw, Kolovou, G, Kong, A, Lambrechts, D, Leander, K, Lieb, W, Lettre, G, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meitinger, T, Melander, O, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Musunuru, K, Nahrstaedt, J, Nöthen, Mm, Olivieri, Oliviero, Peyvandi, F, Patel, Rs, Patterson, Cc, Quyyumi, Aa, Rallidis, Ls, Roosendaal, Fr, Rubin, D, Salomaa, V, Sampietro, Ml, Sandhu, Ms, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, Sm, Siscovick, Ds, Sivananthan, M, Smith, Av, Smith, Tb, Snoep, Jd, Spertus, Ja, Stefansson, K, Stirrups, K, Stoll, M, Tang, Wh, Thorgeirsson, G, Thorleifsson, G, Uitterlinden, Ag, van Rij AM, Voight, Bf, Wareham, Nj, Awells, G, Wichmann, He, Witteman, Jc, Wright, Bj, Ye, S, Quertermous, T, März, W, Blankenberg, S, Roberts, R, Onland Moret NC, van Setten, J, Verschuren, Wm, Boer, Jm, Wijmenga, C, Hofker, Mh, Maitland van der Zee AH, de Boer, A, Grobbee, De, Attwood, T, Belz, S, Braund, P, Cooper, J, Crisp Hihn, A, Foad, N, Gracey, J, Gray, E, Gwilliams, R, Heimerl, S, Jolley, J, Krishnan, U, Lloyd Jones, H, Lugauer, I, Lundmark, P, Moore, Js, Muir, D, Murray, E, Neudert, J, Niblett, D, O'Leary, K, Pollard, H, Rankin, A, Rice, Cm, Sager, H, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Syvannen, Ac, Wallace, C., Cardiologie, RS: CAPHRI School for Public Health and Primary Care, Vascular Medicine, Other departments, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Landsteiner Laboratory, Clinical Haematology, Pulmonology, and Medical Research Council (MRC)
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Male ,Cancer Research ,Candidate gene ,Epidemiology ,Genome-wide association study ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Cardiovascular ,0302 clinical medicine ,GENETICS & HEREDITY ,Genetics (clinical) ,Genetics ,0303 health sciences ,Cardiovascular diseases [NCEBP 14] ,Middle Aged ,3. Good health ,CYP17A1 ,Genetic Epidemiology ,Genome-wide association ,Myocardial-infarction ,Susceptibility loci ,Risk ,Atherosclerosis ,Metanalysis ,Lipoprotein ,Medicine ,Female ,Life Sciences & Biomedicine ,Research Article ,Asian Continental Ancestry Group ,Adult ,SUSCEPTIBILITY LOCI ,lcsh:QH426-470 ,European Continental Ancestry Group ,Biology ,Polymorphism, Single Nucleotide ,coronary artery disease ,genetics ,White People ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Asian People ,Genetic variation ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,Allele ,Molecular Biology ,Gene ,METAANALYSIS ,Ecology, Evolution, Behavior and Systematics ,Genetic Association Studies ,Cardiovascular Disease Epidemiology ,Alleles ,030304 developmental biology ,Aged ,0604 Genetics ,Science & Technology ,Case-control study ,Genetic Variation ,Human Genetics ,Odds ratio ,large-scale gene analysis ,lcsh:Genetics ,LIPOPROTEIN ,MYOCARDIAL-INFARCTION ,ATHEROSCLEROSIS ,Case-Control Studies ,Genetics of Disease ,IBC 50K CAD Consortium ,Developmental Biology ,Genome-Wide Association Study - Abstract
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p, Author Summary Coronary artery disease (CAD) has a strong genetic basis that remains poorly characterised. Using a custom-designed array, we tested the association with CAD of almost 50,000 common and low frequency variants in ∼2,000 genes of known or suspected cardiovascular relevance. We genotyped the array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin) and attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. We report the novel association of variants in or near four genes with CAD and in additional studies identify potential mechanisms by which some of these novel variants affect CAD risk. Interestingly, we found that these variants, as well as the majority of previously reported CAD variants, have similar associations in Europeans and South Asians. Contrary to prior expectations, many previously suggested candidate genes did not show evidence of any effect on CAD risk, and neither did we identify any novel low frequency alleles with strong effects amongst the genes tested. Discovery of novel genes associated with heart disease may help to further understand the aetiology of cardiovascular disease and identify new targets for therapeutic interventions.
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- 2016
11. Hypothesis-based analysis of gene-gene interactions and risk of myocardial infarction
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Lucas G1, Lluís-Ganella C, Subirana I, Musameh MD, Gonzalez JR, Nelson CP, Sentí M, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Schwartz SM, Siscovick D, O'Donnell CJ, Melander O, Salomaa V, Purcell S, Altshuler D, Samani NJ, Kathiresan S, Elosua R, Voight BF, Musunuru K, Ardissino D, Mannucci PM, Anand S, Engert JC, Schunkert H, Erdmann J, Reilly MP, Rader DJ, Morgan T, Spertus JA, Stoll M, Girelli D, McKeown PP, Patterson CC, Siscovick DS, Peltonen L, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Yee J, Friedlander Y, Marrugat J, Lucas G, Sala J, Ramos R, Meigs JB, Williams G, Nathan DM, MacRae CA, Havulinna AS, Berglund G, Deloukas P, Donnelly P, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Kwiatkowski DP, Mathew CG, McCarthy MI, Ouwehand WH, Parkes M, Pembrey M, Rahman N, Stratton MR, Todd JA, Worthington J, Burton PR, Clayton DG, Cardon LR, Craddock N, Duncanson A, Barrett JC, Davison D, Easton D, Evans D, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Ball SG, Balmforth AJ, Barrett JH, Bishop D, Iles MM, Maqbool A, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Cardo LR, Cardin NJ, Ferreira T, Pereira-Gale J, Hallgrimsdottir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Lucas, G1, Lluís-Ganella, C, Subirana, I, Musameh, Md, Gonzalez, Jr, Nelson, Cp, Sentí, M, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Schwartz, Sm, Siscovick, D, O'Donnell, Cj, Melander, O, Salomaa, V, Purcell, S, Altshuler, D, Samani, Nj, Kathiresan, S, Elosua, R, Voight, Bf, Musunuru, K, Ardissino, D, Mannucci, Pm, Anand, S, Engert, Jc, Schunkert, H, Erdmann, J, Reilly, Mp, Rader, Dj, Morgan, T, Spertus, Ja, Stoll, M, Girelli, D, Mckeown, Pp, Patterson, Cc, Peltonen, L, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Lucas, G, Sala, J, Ramos, R, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, Havulinna, A, Berglund, G, Deloukas, P, Donnelly, P, Farrall, M, Gough, Sc, Hall, A, Hattersley, At, Hill, Av, Kwiatkowski, Dp, Mathew, Cg, Mccarthy, Mi, Ouwehand, Wh, Parkes, M, Pembrey, M, Rahman, N, Stratton, Mr, Todd, Ja, Worthington, J, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Duncanson, A, Barrett, Jc, Davison, D, Easton, D, Evans, D, Leung, Ht, Marchini, Jl, Morris, Ap, Spencer, Cc, Tobin, Md, Attwood, Ap, Boorman, Jp, Cant, B, Everson, U, Hussey, Jm, Jolley, Jd, Knight, A, Koch, K, Meech, E, Nutland, S, Prowse, Cv, Stevens, He, Taylor, Nc, Walters, Gr, Walker, Nm, Watkins, Na, Winzer, T, Jones, Rw, Mcardle, Wl, Ring, Sm, Strachan, Dp, Ball, Sg, Balmforth, Aj, Barrett, Jh, Bishop, D, Iles, Mm, Maqbool, A, Braund, P, Dixon, Rj, Mangino, M, Stevens, S, Thompson, Jr, Bumpstead, Sj, Chaney, A, Downes, K, Ghori, Mj, Gwilliam, R, Hunt, Se, Inouye, M, Keniry, A, King, E, Mcginnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Cardo, Lr, Cardin, Nj, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, Ib, Howie, Bn, Su, Z, Teo, Yy, and Vukcevic, D
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Heredity ,Epidemiology ,Myocardial Infarction ,lcsh:Medicine ,Genome-wide association study ,Coronary Artery Disease ,Cardiovascular ,Logistic regression ,Risk Factors ,Cardiac and Cardiovascular Systems ,lcsh:Science ,Genetics ,0303 health sciences ,Multidisciplinary ,Medicine (all) ,030305 genetics & heredity ,Genomics ,Genetic Epidemiology ,Medicine ,Research Article ,Human ,Risk ,Genotype ,Genotypes ,Reproducibility of Result ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Genome Analysis Tools ,Genome-Wide Association Studies ,Humans ,Genetic Predisposition to Disease ,Risk factor ,Allele frequency ,Genetic Association Studies ,030304 developmental biology ,Genetic association ,Biochemistry, Genetics and Molecular Biology (all) ,Complex Traits ,Risk Factor ,lcsh:R ,Reproducibility of Results ,Human Genetics ,Epistasis, Genetic ,Odds ratio ,Genetic epidemiology ,Agricultural and Biological Sciences (all) ,Genetics of Disease ,Epistasis ,Genetic Polymorphism ,Infart de miocardi -- Epidemiologia ,lcsh:Q ,Population Genetics ,Genome-Wide Association Study - Abstract
The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3–2.0, depending on allele frequency and interaction model).
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- 2012
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12. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
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Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ, Qasim AN, DerOhannessian SL, Qu L, Cappola TP, Chen Z, Matthai W, Hakonarson HH, Wilensky R, Kent KM, Lindsay JM, Pichard AD, Satler L, Waksman R, Knoupf CW, Walker MC, Waterworth DM, Mosser V, Braund PS, Wright B, Balmforth AJ, Ball SG, Chen L, Wells GA, McPherson R, Lackner K, Munzel TF, Schillert A, Schnabel R, Zeller T, Ziegler A, Absher D, Hlatky MA, Iribaren C, Knowles JW, Linsel Nitschke P, König IR, Hengstenberg C, Nahrstaedt J, Peters A, Schreiber S, Wichmann E, Willenborg C, Su S, Bouzyk M, Vaccarino V, Zafari AM, Carlquist JF, Muhlestein JB, Olivieri O, Barnard J, Hartiala J, Tang WH, Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Dixon RJ, Mangino M, Stevens S, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop M, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Ferreira T, Pereira Gale J, Hallgrimsdóttir IB, Bowie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Meigs JB, Williams G, Nathan DM, MacRae CA, O'Donnell CJ, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, CASARI , GIORGIO NEVIO, Reilly, Mp, Li, M, He, J, Ferguson, Jf, Stylianou, Im, Mehta, Nn, Burnett, M, Devaney, Jm, Knouff, Cw, Thompson, Jr, Horne, Bd, Stewart, Af, Assimes, Tl, Wild, P, Allayee, H, Nitschke, Pl, Patel, R, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Martinelli, N, Girelli, D, Quyyumi, Aa, Anderson, Jl, Erdmann, J, Hall, A, Schunkert, H, Quertermous, T, Blankenberg, S, Hazen, Sl, Roberts, R, Kathiresan, S, Samani, Nj, Epstein, Se, Rader, Dj, Qasim, An, Derohannessian, Sl, Qu, L, Cappola, Tp, Chen, Z, Matthai, W, Hakonarson, Hh, Wilensky, R, Kent, Km, Lindsay, Jm, Pichard, Ad, Satler, L, Waksman, R, Knoupf, Cw, Walker, Mc, Waterworth, Dm, Mosser, V, Braund, P, Wright, B, Balmforth, Aj, Ball, Sg, Chen, L, Wells, Ga, Mcpherson, R, Lackner, K, Munzel, Tf, Schillert, A, Schnabel, R, Zeller, T, Ziegler, A, Absher, D, Hlatky, Ma, Iribaren, C, Knowles, Jw, Linsel Nitschke, P, König, Ir, Hengstenberg, C, Nahrstaedt, J, Peters, A, Schreiber, S, Wichmann, E, Willenborg, C, Su, S, Bouzyk, M, Vaccarino, V, Zafari, Am, Carlquist, Jf, Muhlestein, Jb, Olivieri, O, Barnard, J, Hartiala, J, Tang, Wh, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Deloukas, P, 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R, Hunt, Se, Inouye, M, Keniry, A, King, E, Mcginnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, Nj, Ferreira, T, Pereira Gale, J, Hallgrimsdóttir, Ib, Bowie, Bn, Su, Z, Teo, Yy, Vukcevic, D, Bentley, D, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, O'Donnell, Cj, Ardissino, D, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, GIORGIO NEVIO, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Mannucci, Pm, Schwartz, Sm, Siscovick, D, Yee, J, Friedlander, Y, Elosua, R, Marrugat, J, Lucas, G, Subirana, I, Sala, J, Ramos, R, Salomaa, V, Havulinna, A, Peltonen, L, Melander, O, Berglund, G, Voight, Bf, Hirschhorn, Jn, Asselta, R, Duga, S, Spreafico, M, Musunuru, K, Daly, Mj, Purcell, S, Surti, A, Guiducci, C, Gianniny, L, Mirel, D, Parkin, M, Burtt, N, and Gabriel, Sb
- Subjects
Adult ,Male ,medicine.medical_specialty ,Linkage disequilibrium ,ABO ,ADAMTS7 Protein ,ADAMTS7 ,Genome-wide association study ,Coronary Angiography ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,ABO Blood-Group System ,Coronary artery disease ,Gene Frequency ,ABO blood group system ,Internal medicine ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Myocardial infarction ,Genetic risk factor ,genetic locus ,Coronary atherosclerosis ,Aged ,business.industry ,coronary atherosclerosis ,General Medicine ,Middle Aged ,medicine.disease ,ADAM Proteins ,myocardial infarction ,Genetic Loci ,Cardiology ,Myocardial infarction complications ,Female ,business ,coronary artery disease ,Genome-Wide Association Study - Abstract
BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. METHODS: We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). FINDINGS: In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. INTERPRETATION: Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. FUNDING: The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
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- 2011
13. Common polymorphisms of [beta].sub.1-adrenoceptor: identification and rapid screening assay
- Author
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Maqbool, A., Hall, AS, Ball, SG, and Balmforth, AJ
- Published
- 1999
14. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.
- Author
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ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, 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Cornelis, M.C., Ciullo, M., Pirastu, M., de Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L., Ulivi, S., Hwang, S.J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., de Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H., Fox, C.S., ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, NL., Go, MJ., Goel, A., Grässler, J., Grobbee, DE., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, BG., Hardy, R., Hartikainen, AL., Heath, S., Heckbert, SR., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, AA., Hilton, G., Hingorani, AD., Bolton, JA., Hopewell, JC., Howard, P., Humphries, SE., Hunt, SC., Hveem, K., Ikram, MA., Islam, M., Iwai, N., Jarvelin, MR., Jackson, AU., Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., Watkins, H., Weder, AB., Whincup, PH., Wiggins, KL., Witteman, JC., Wong, A., Wu, Y., Yajnik, CS., Yao, J., Young, JH., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, JH., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, JY., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, SC., Wong, TY., Liu, J., Young, TL., Aung, T., Teo, YY., Kim, YJ., Kang, D., Chen, CH., Tsai, FJ., Chang, LC., Fann, SJ., Mei, H., Hixson, JE., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, YT., Tanaka, T., Reilly, MP., Schunkert, H., Assimes, TL., Hall, A., Hengstenberg, C., König, IR., Laaksonen, R., McPherson, R., Thompson, JR., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, LA., Halperin, E., Li, M., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, GA., Holm, H., Roberts, R., Stewart, AF., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, KJ., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, HJ., Perret, C., Proust, C., Münzel, TF., Barbalic, M., Chen, IY., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, KD., Volcik, K., Gretarsdottir, S., Gulcher, JR., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, AK., Willenborg, C., Böhm, BO., Dobnig, H., Grammer, TB., Hoffmann, MM., Meinitzer, A., Winkelmann, BR., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, SB., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Epstein, SE., Rader, DJ., Nelson, CP., Wright, BJ., Balmforth, AJ., Ball, SG., Loehr, LR., Rosamond, WD., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, YA., Stricker, BH., Chang, PP., Willerson, JT., Felix, SB., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, RJ., Greiser, KH., Deckers, JW., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, MM., Werdan, K., Mitchell, GF., Arnett, DK., Gottdiener, JS., Blettner, M., Friedrich, N., Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.H., Pers, T.H., Johnson, A.D., Ko, Y.A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., d'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., van der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.C., Stafford, J.M., Gaspoz, J.M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., de Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L., Ulivi, S., Hwang, S.J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., de Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H., and Fox, C.S.
- Abstract
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
- Published
- 2016
15. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
- Author
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Jostins, Luke, Ripke, Stephan, Weersma, Rinse K., Duerr, Richard H., Mcgovern, Dermot P., Hui, Ken Y., Lee, James C., Philip Schumm, L., Sharma, Yashoda, Anderson, Carl A., Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L., Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Andrews, Jane M., Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A., Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D'Amato, Mauro, De Jong, Dirk, Devaney, Kathy L., Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R., Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Xinli, Hu, Karlsen, Tom H., Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R., Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Regueiro, Miguel, Rotter, Jerome I., Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A., Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kent D., Tremelling, Mark, Verspaget, Hein W., De Vos, Martine, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhao, Hongyu, Silverberg, Mark S., Annese, Vito, Hakonarson, Hakon, Brant, Steven R., Radford Smith, Graham, Mathew, Christopher G., Rioux, John D., Schadt, Eric E., Daly, Mark J., Franke, Andre, Parkes, Miles, Vermeire, Severine, Barrett, Jeffrey C., Cho, Judy H., Barclay, M, Peyrin Biroulet, L, Chamaillard, M, Colombel, Jf, Cottone, M, Croft, A, D'Incà, R, Halfvarson J, Hanigan K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lémann, M, Levine, A, Massey, D, Milla, M, Montgomery, Gw, Ng, Sm, Oikonomou, I, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, Laura, Taylor, Km, Törkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Andrews, Jm, Bampton, Pa, Florin, Th, Gearry, R, Krishnaprasad, K, Lawrance, Ic, Mahy, G, Radford Smith, G, Roberts, Rl, Simms, La, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie AM 3rd, Beck, K, Bernard, Ej, Binion, Dg, Bitton, A, Brant, Sr, Cho, Jh, Cohen, A, Croitoru, K, Daly, Mj, Datta, Lw, Deslandres, C, Duerr, Rh, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, Gr, Haritunians, T, Jobin, G, Katz, S, Lahaie, Rg, Mcgovern, Dp, Nelson, L, Ning, K, Paré, P, Regueiro, Md, Rioux, Jd, Ruggiero, E, Schumm, L, Schwartz, M, Scott, R, Sharma, Y, Silverberg, Ms, Spears, D, Steinhart, A, Stempak, Jm, Swoger, Jm, Tsagarelis, C, Zhang, C, Zhao, H, Aerts, J, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, Sg, Balmforth, Aj, Barnes, C, Barrett, Jc, Barroso, I, Barton, A, Bennett, Aj, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, Oj, Braund, Ps, Bredin, F, Breen, G, Brown, Mj, Bruce, In, Bull, J, Burren, Os, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, Cm, Coffey, Aj, Connell, Jm, Conrad, Df, Cooper, Jd, Dominiczak, Af, Downes, K, Drummond, He, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, Dm, Evans, G, Eyre, S, Farmer, A, Ferrier, In, Flynn, E, Forbes, A, Forty, L, Franklyn, Ja, Frayling, Tm, Freathy, Rm, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon Smith, K, Gray, E, Green, E, Groves, Cj, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, Ga, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, Jm, Hughes, D, Hunt, S, Isaacs, Jd, Jain, M, Jewell, Dp, Johnson, T, Jolley, Jd, Jones, Ir, Jones, La, Kirov, G, Langford, Cf, Lango Allen, H, Lathrop, Gm, Lee, J, Lee, Kl, Lees, C, Lewis, K, Lindgren, Cm, Maisuria Armer, M, Maller, J, Mansfield, J, Marchini, Jl, Martin, P, Massey, Dc, Mcardle, Wl, Mcguffin, P, Mclay, Ke, Mcvean, G, Mentzer, A, Mimmack, Ml, Morgan, Ae, Morris, Ap, Mowat, C, Munroe, Pb, Myers, S, Newman, W, Nimmo, Er, O'Donovan, Mc, Onipinla, A, Ovington, Nr, Owen, Mj, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, Jr, Phillips, A, Plagnol, V, Prescott, Nj, Prokopenko, I, Quail, Ma, Rafelt, S, Rayner, Nw, Reid, Dm, Renwick, A, Ring, Sm, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, Jg, Sanderson, Jd, Sawcer, Sj, Schuilenburg, H, Scott, Ce, Seal, S, Shaw Hawkins, S, Shields, Bm, Simmonds, Mj, Smyth, Dj, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, He, Stirrups, K, Stone, Ma, Strachan, Dp, Su, Z, Symmons, Dp, Thompson, Jr, Thomson, W, Tobin, Md, Travers, Me, Turnbull, C, Vukcevic, D, Wain, Lv, Walker, M, Walker, Nm, Wallace, C, Warren Perry, M, Watkins, Na, Webster, J, Weedon, Mn, Wilson, Ag, Woodburn, M, Wordsworth, Bp, Yau, C, Young, Ah, Zeggini, E, Brown, Ma, Burton, Pr, Caulfield, Mj, Compston, A, Farrall, M, Gough, Sc, Hall, As, Hattersley, At, Hill, Av, Mathew, Cg, Pembrey, M, Satsangi, J, Stratton, Mr, Worthington, J, Hurles, Me, Duncanson, A, Ouwehand, Wh, Parkes, M, Rahman, N, Todd, Ja, Samani, Nj, Kwiatkowski, Dp, Mccarthy, Mi, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, Jm, Bramon, E, Casas, Jp, Corvin, A, Jankowski, J, Markus, Hs, Palmer, Cn, Plomin, R, Rautanen, A, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
- Subjects
Genome-wide association study ,Disease ,SUSCEPTIBILITY ,Inflammatory bowel disease ,NUMBER ,0302 clinical medicine ,Crohn Disease ,NETWORK ,Genetics ,0303 health sciences ,Multidisciplinary ,Genomics ,Ulcerative colitis ,3. Good health ,Colitis, Ulcerative ,Genetic Predisposition to Disease ,Genome, Human ,Haplotypes ,Humans ,Inflammatory Bowel Diseases ,Mycobacterium ,Mycobacterium Infections ,Mycobacterium tuberculosis ,Phenotype ,Polymorphism, Single Nucleotide ,Reproducibility of Results ,Genome-Wide Association Study ,Host-Pathogen Interactions ,IRGM ,Medical genetics ,030211 gastroenterology & hepatology ,EXPRESSION ,medicine.medical_specialty ,Immunology ,Biology ,Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2] ,TUBERCULOSIS ,03 medical and health sciences ,Medical research ,medicine ,Allele ,METAANALYSIS ,030304 developmental biology ,HYPER-IGE SYNDROME ,MUTATIONS ,medicine.disease ,RISK LOCI ,Genetic architecture ,digestive system diseases - Abstract
Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
- Published
- 2012
- Full Text
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16. Homocysteine and coronary heart disease: Meta-analysis of MTHFR case-control studies, avoiding publication bias
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Holm, H, Thorsteinsdottir, U, Gretarsdottir, S, Gulcher, Jr, Thorgeirsson, G, Andersen, K, Stefansson, K, Parish, S, Bennett, Da, Clarke, R, Peto, R, Sleight, P, Collins, R, Hopewell, Jc, Watkins, H, Saleheen, D, Danesh, J, Rasheed, A, Zaidi, M, Frossard, P, Shah, N, Samuel, M, Tanaka, T, Ozaki, K, Sato, H, Sakata, Y, Komuro, I, Anand, Ss, Yusuf, S, Engert, Jc, Chambers, J, Kooner, J, Armitage, J, Samani, Nj, Braund, Ps, Nelson, Cp, Hall, As, Balmforth, A, Ball, Sg, Kleber, Me, Hoffmann, Mm, März, Wa, Bugert, P, Winkelmann, B, Böhm, Bo, Ouwehand, Wh, Sivapalaratnam, S, Kastelein, Jj, Trip, Md, Bezzina, Cr, Ouwehand, W, Yamada, Y, Elbers, Cc, Onland Moret NC, Bauer, F, van der Schouw YT, Verschuren, Wm, de Boer JM, Wijmenga, C, Hofker, Mh, de Bakker PI, Peters, Bj, Maitland van der Zee AH, de Boer, A, Klungel, Oh, Grobbee, De, Stewart, Af, Roberts, R, Mcpherson, R, Chen, L, Wells, Ga, Reilly, Mm, Li, M, Qu, I, Rader, Dj, Thorand, B, Illig, T, Peters, A, Koenig, W, Assimes, Tl, Fortmann, S, Iribarren, C, Abbate, R, Marcucci, R, Anderson, Jl, Zebrack, Js, Ardissino, D, Merlini, Fm, Bonomi, Ab, Ashfield Watt PA, Clark, Ze, van Bockxmeer FM, Brownrigg, L, Kooner, Js, Ferrer Antunes, C, Palmeiro, A, Fernandez Arcas, N, Reyes Engel, A, Folsom, Ar, Fowkes, Fg, Lee, Aj, Gaziano, Jm, Gemmati, D, Scapoli, Gl, Genest, J, Rozen, R, Girelli, Domenico, Corrocher, Roberto, Rossi, Gb, Meleady, R, Graham, Im, Gulec, S, Hopkins, Pn, Inbal, A, Selighson, U, Jukema, Jw, Litynsky, P, Kluijtmans, La, Kozich, V, Janosikova, B, Ma, J, Stampfer, Mj, Malinow, Mr, Meisel, C, Stangl, K, Morita, H, Nagai, R, Nakai, K, Nordestgaard, Bg, Zacho, J, Rimm, Eb, Schwartz, Sm, Siscovick, Ds, Silberberg, Js, Szczeklik, A, Domagala, Bt, Tanis, Bc, Rosendaal, Fm, Thogersen, Am, Nilsson, Tk, Todesco, L, Tokgozoglu, Sl, Tsai, My, Hanson, Nq, Verhoeff, Bj, Yamakawa Kobayashi, K, Hamaguchi, H., Medical Research Council (MRC), Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Pulmonology, and Other departments
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Homocysteine ,coronary heart disease ,methylene tetrahydrofolate reductase ,Coronary Disease ,FOLIC-ACID ,030204 cardiovascular system & hematology ,PLACEBO-CONTROLLED TRIAL ,Gastroenterology ,Methylenetetrahydrofolate reductase gene ,Placebo-controlled trial ,Cardiovascular-disease ,Mendelian randomization ,Myocardial-infarction ,Vascular-disease ,Common mutation ,B vitamins ,Folic-acid ,Ethnic-groups ,chemistry.chemical_compound ,MTHFR ,risk factors ,publication bias ,GWA ,genome-wide association ,meta-analysis ,0302 clinical medicine ,Polymorphism (computer science) ,030212 general & internal medicine ,Myocardial infarction ,11 Medical and Health Sciences ,Genetics ,biology ,VASCULAR-DISEASE ,General Medicine ,ETHNIC-GROUPS ,3. Good health ,CARDIOVASCULAR-DISEASE ,Meta-analysis ,MENDELIAN RANDOMIZATION ,Medicine ,MTHFR Studies Collaborative Group ,Life Sciences & Biomedicine ,Research Article ,medicine.medical_specialty ,Genotype ,METHYLENETETRAHYDROFOLATE REDUCTASE GENE ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,03 medical and health sciences ,Medicine, General & Internal ,Folic Acid ,Bias ,Internal medicine ,General & Internal Medicine ,medicine ,Humans ,Methylenetetrahydrofolate Reductase (NADPH2) ,Science & Technology ,Polymorphism, Genetic ,business.industry ,Case-control study ,Odds ratio ,Publication bias ,medicine.disease ,COMMON MUTATION ,chemistry ,MYOCARDIAL-INFARCTION ,Methylenetetrahydrofolate reductase ,biology.protein ,B VITAMINS ,business - Abstract
Robert Clarke and colleagues conduct a meta-analysis of unpublished datasets to examine the causal relationship between elevation of homocysteine levels in the blood and the risk of coronary heart disease. Their data suggest that an increase in homocysteine levels is not likely to result in an increase in risk of coronary heart disease., Background Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality. Methods and Findings Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR, Editors' Summary Background Coronary heart disease (CHD) is the leading cause of death among adults in developed countries. With age, fatty deposits (atherosclerotic plaques) coat the walls of the coronary arteries, the blood vessels that supply the heart with oxygen and nutrients. The resultant restriction of the heart's blood supply causes shortness of breath, angina (chest pains that are usually relieved by rest), and sometimes fatal heart attacks. Many established risk factors for CHD, including smoking, physical inactivity, being overweight, and eating a fat-rich diet, can be modified by lifestyle changes. Another possible modifiable risk factor for CHD is a high blood level of the amino acid homocysteine. Methylene tetrahydofolate reductase, which is encoded by the MTHFR gene, uses folate to break down and remove homocysteine so fortification of cereals with folate can reduce population homocysteine blood levels. Pooled results from prospective observational studies that have looked for an association between homocysteine levels and later development of CHD suggest that the reduction in homocysteine levels that can be achieved by folate supplementation is associated with an 11% lower CHD risk. Why Was This Study Done? Prospective observational studies cannot prove that high homocysteine levels cause CHD because of confounding, the potential presence of other unknown shared characteristics that really cause CHD. However, an approach called “Mendelian randomization” can test whether high blood homocysteine causes CHD. A common genetic variant of the MTHFR gene—the C677T polymorphism—reduces MTHFR efficiency so TT homozygotes (individuals in whom both copies of the MTHFR gene have the nucleotide thymine at position 677; the human genome contains two copies of most genes) have 25% higher blood homocysteine levels than CC homozygotes. In meta-analyses (statistical pooling of the results of several studies) of published Mendelian randomized studies, TT homozygotes have a higher CHD risk than CC homozygotes. Because gene variants are inherited randomly, they are not subject to confounding, so this result suggests that high blood homocysteine causes CHD. But what if only Mendelian randomization studies that found an association have been published? Such publication bias would affect this aggregate result. Here, the researchers investigate the association of the MTHFR C677T polymorphism with CHD in unpublished datasets that have analyzed this polymorphism incidentally during other genetic studies. What Did the Researchers Do and Find? The researchers obtained 19 unpublished datasets that contained data on the MTHFR C677T polymorphism in thousands of people with and without CHD. Meta-analysis of these datasets indicates that the excess CHD risk in TT homozygotes compared to CC homozygotes was 2% (much lower than predicted from the prospective observational studies), a nonsignificant difference (that is, it could have occurred by chance). When the probable folate status of the study populations (based on when national folic acid fortification legislation came into effect) was taken into account, there was still no evidence that TT homozygotes had an excess CHD risk. By contrast, in an updated meta-analysis of 86 published studies of the association of the polymorphism with CHD, the excess CHD risk in TT homozygotes compared to CC homozygotes was 15%. Finally, in a meta-analysis of randomized trials on the use of vitamin B supplements for homocysteine reduction, folate supplementation had no significant effect on the 5-year incidence of CHD. What Do These Findings Mean? These analyses of unpublished datasets are consistent with lifelong moderate elevation of homocysteine levels having no significant effect on CHD risk. In other words, these findings indicate that circulating homocysteine levels within the normal range are not causally related to CHD risk. The meta-analysis of the randomized trials of folate supplementation also supports this conclusion. So why is there a discrepancy between these findings and those of meta-analyses of published Mendelian randomization studies? The discrepancy is too large to be dismissed as a chance finding, suggest the researchers, but could be the result of publication bias—some studies might have been prioritized for publication because of the positive nature of their results whereas the unpublished datasets used in this study would not have been affected by any failure to publish null results. Overall, these findings reveal a serious example of publication bias and argue against the use of folate supplements as a means of reducing CHD risk. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001177. The American Heart Association provides information about CHD and tips on keeping the heart healthy; it also provides information on homocysteine, folic acid, and CHD, general information on supplements and heart health, and personal stories about CHD The UK National Health Service Choices website provides information about CHD, including personal stories about CHD Information is available from the British Heart Foundation on heart disease and keeping the heart healthy The US National Heart Lung and Blood Institute also provides information on CHD (in English and Spanish) MedlinePlus provides links to many other sources of information on CHD (in English and Spanish) Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
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- 2012
17. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes
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Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, Bouatia Naji, N, Dimas, As, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, Cs, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, Kerr Conte, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, Martínez Larrad MT, Narisu, N, Nastase Mannila, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, van 't Hooft FM, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, Serrano Ríos, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, Fs, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, Voight BF, Florez J. C., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, P, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Franklin, Cs, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Nilsson, P, Owen, Kr, Perry, Jr, Petersen, K, Platou, C, Proença, C, Rathmann, W, William Rayner, N, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Thorand, B, Tichet, J, van Dam RM, van Haeften TW, van Herpt, T, van Vliet JV, Bragi Walters, G, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Pankow, Js, Pedersen, O, Wichmann, E, Florez, Jc, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Stefansson, K, Altshuler, D, Speliotes, Ek, Berndt, Si, Monda, Kl, Allen, Hl, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Workalemahu, T, Heid, Im, Wood, Ar, Weyant, Rj, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Kilpeläinen, To, Yang, J, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, Heard Costa NL, Hoesel, V, Hottenga, Jj, Johansson, Å, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Timpson, Nj, Tyrer, Jp, van Wingerden, S, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Arnold, Am, Aspelund, T, Atwood, Ld, Balmforth, Aj, Ben Shlomo, Y, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Cappuccio, Fp, Cavalcanti Proença, C, Ida Chen YD, Chen, Cm, Coin, L, Connell, J, Day, In, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Facheris, Mf, Felix, Sb, Fischer Posovszky, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gjesing, Ap, Goyette, P, Grässler, J, Greenawalt, Dm, Gudnason, V, Hartikainen, Al, Hall, As, Havulinna, As, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jousilahti, P, Jula, A, Kaakinen, M, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Terho, L, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, P, Marek, D, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Melander, O, Meyre, D, Montgomery, Gw, Mulic, R, Ngwa, Js, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, Ms, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, Ds, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Tammesoo, Ml, Tardif, Jc, Teder Laving, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, van Meurs JB, van Ommen GJ, Vatin, V, Viikari, J, Visvikis Siest, S, Vitart, V, Vogel, Ci, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, Is, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, Ms, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, Js, Boeing, H, Dorret, I. B., Caulfield, Mj, Chanock, Sj, Cupples, La, Smith, Gd, Erdmann, J, Grönberg, H, Hall, P, Harris, Tb, Hayes, Rb, Heinrich, J, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Penninx, Bw, Peters, A, Quertermous, T, Reinehr, T, Rissanen, A, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Uda, M, Valle, Tt, Wabitsch, M, Waeber, G, Shaun, P, Eric, E. S., Peter, M. V., Assimes, Tl, Borecki, Ib, Groop, Lc, Haritunians, T, Kaplan, Rc, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, van Duijn CM, Barroso, H, North, Ke, Hirschhorn, Jn, Nica, Ac, Parts, L, Glass, D, Nisbet, J, Barrett, A, Sekowska, M, Travers, M, Potter, S, Grundberg, E, Small, K, Hedman, Åk, Bataille, V, Bell, Jt, Surdulescu, G, Ingle, C, Nestle, Fo, di Meglio, P, Min, Jl, Wilk, A, Hammond, Cj, Yang, Tp, Montgomery, Sb, Zondervan, Kt, Durbin, R, Ahmadi, K, Reilly, Mp, Holm, H, Stewart, Af, Barbalic, M, Absher, D, Aherrahrou, Z, Allayee, H, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Braund, Ps, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari NE, Ellis, Sg, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Horne, Bd, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kastelein, Jj, Kolovou, G, Laaksonen, R, Lambrechts, D, Leander, K, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Sampietro, Ml, Schadt, E, Schäfer, A, Schillert, A, Schrezenmeir, J, Schwartz, Sm, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Spertus, Ja, Stark, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Wright, Bj, Ye, S, Zeller, T, Cambien, F, Goodall, Ah, März, W, Blankenberg, S, Roberts, R, Mcpherson, R, Nilesh, J. S., Medical Research Council (MRC), Nica, Alexandra, Ongen, Halit, Dermitzakis, Emmanouil, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Scherag, Andre (Beitragende*r), Hinney, Anke (Beitragende*r), Scherag, S. (Beitragende*r), Vogel, C (Beitragende*r), Hebebrand, Johannes (Beitragende*r), University of Groningen, Wheeler, Eleanor [0000-0002-8616-6444], Barnes, Daniel [0000-0002-3781-7570], Luan, Jian'an [0000-0003-3137-6337], Johnson, Kathleen [0000-0002-6823-3252], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository
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Male ,Netherlands Twin Register (NTR) ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Medizin ,Genome-wide association study ,Type 2 diabetes ,CORONARY HEART-DISEASE ,Fasting/blood ,0302 clinical medicine ,Insulin ,Glucose homeostasis ,ddc:576.5 ,Genome-wide ,Diabetes Mellitus, Type 2/blood/genetics/metabolism ,CARDIoGRAM Consortium ,POPULATION ,Proinsulin ,RISK ,Genetics ,0303 health sciences ,INSULIN SENSITIVITY ,11 Medical And Health Sciences ,Fasting ,Polymorphism, Single Nucleotide/genetics ,OBESITY ,Female ,type 2 diabetes ,Life Sciences & Biomedicine ,hormones, hormone substitutes, and hormone antagonists ,Insulin processing ,Adult ,medicine.medical_specialty ,endocrine system ,ENDOCRINOLOGY & METABOLISM ,SUSCEPTIBILITY LOCI ,Genotype ,030209 endocrinology & metabolism ,DIAGRAM Consortium ,Biology ,C4D Consortium ,Polymorphism, Single Nucleotide ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Insulin resistance ,BETA-CELL FUNCTION ,SDG 3 - Good Health and Well-being ,Internal medicine ,GIANT Consortium ,Internal Medicine ,medicine ,Humans ,METAANALYSIS ,030304 developmental biology ,Science & Technology ,Genome, Human ,Hormonal regulation [IGMD 6] ,Genetic Variation ,nutritional and metabolic diseases ,proinsulin ,medicine.disease ,Proinsulin/blood ,TCF7L2 ,Endocrinology ,Diabetes Mellitus, Type 2 ,MuTHER Consortium ,GLUCOSE-HOMEOSTASIS ,Insulin/blood - Abstract
OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.
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- 2011
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18. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
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Schunkert, H, König, Ir, Kathiresan, S, Reilly, Mp, Assimes, Tl, Holm, H, Preuss, M, Stewart, Af, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Balmforth, Aj, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Boerwinkle, E, Braund, Ps, Brown, Mj, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, Mokhtari, Ne, Ellis, Sg, Elosua, R, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Folsom, Ar, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gudnason, V, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Hofman, A, Horne, Bd, Illig, T, Iribarren, C, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kaplan, Lm, Kastelein, Jj, Khaw, Kt, Knowles, Jw, Kolovou, G, Kong, A, Laaksonen, R, Lambrechts, D, Leander, K, Lettre, G, Li, M, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Meitinger, T, Melander, O, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peters, A, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Salomaa, V, Sampietro, Ml, Sandhu, Ms, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, Sm, Siscovick, Ds, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Soranzo, N, Spertus, Ja, Stark, K, Stirrups, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Thorleifsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Voight, Bf, Wareham, Nj, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Witteman, Jc, Wright, Bj, Ye, S, Zeller, T, Ziegler, A, Cambien, F, Goodall, Ah, Cupples, La, Quertermous, T, März, W, Hengstenberg, C, Blankenberg, S, Ouwehand, Wh, Hall, As, Deloukas, P, Thompson, Jr, Stefansson, K, Roberts, R, Thorsteinsdottir, U, O'Donnell, Cj, Mcpherson, R, Erdmann, J, the CARDIoGRAM Consortium, Samani, N. J., Epidemiology, Internal Medicine, ACS - Amsterdam Cardiovascular Sciences, Cardiology, and Vascular Medicine
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Adult ,Male ,Multifunction cardiogram ,Locus (genetics) ,Single-nucleotide polymorphism ,Genome-wide association study ,Coronary Artery Disease ,Biology ,Polymorphism, Single Nucleotide ,Genetic determinism ,artery disease ,Article ,Coronary artery disease ,Gene Frequency ,SDG 3 - Good Health and Well-being ,Risk Factors ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Allele ,Genotyping ,Allele frequency ,coronary ,Alleles ,Genetics (clinical) ,Aged ,Genetic association ,business.industry ,Case-control study ,Middle Aged ,medicine.disease ,coronary artery disease ,Large-scale association analysis ,Case-Control Studies ,Female ,Cardiology and Cardiovascular Medicine ,business ,Genome-Wide Association Study - Abstract
1. The CARDIoGRAM Consortium. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nature Genetics. 2011;43:333–338. ### Study Hypothesis Recently, genome-wide association studies (GWAS) have identified several common variants that are associated with risk of coronary artery disease (CAD) and myocardial infarction (MI). The authors state that the current loci discovered in CAD and MI GWAS explain only a small fraction of the heritability of this complex disease. The authors hypothesized that a larger study would provide more power to discover common variants with modest effect sizes. Therefore, they formed the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium, which consisted of data from 14 GWAS of CAD and MI.1 ### How Was the Hypothesis Tested? The authors performed a meta-analysis of 14 GWAS of CAD comprising 22 233 cases and 64 762 control subjects, all of European ancestry. CAD was defined angiographically in a subset (n=7364) and by history in the entire sample. Presence of MI ranged from 48.1% to 100% of each cohort. After the meta-analysis, they genotyped the lead single-nucleotide polymorphisms (SNPs) within the most promising (defined a priori as P 90% power to detect effect sizes observed in the GWAS meta-analysis. Finally, to understand potential mechanisms and intermediate pathways by which novel loci may mediate risk, the authors interrogated 3 genome-wide studies that also assessed gene expression in multiple tissues, using human cell lines, a genome-wide map of allelic expression imbalance, and other human disease traits. ### Principal Findings The analysis of approximately 135 000 individuals more than doubled the number of loci with CAD association, yielding 13 previously unidentified loci and confirming at …
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- 2011
19. British society for matrix biology autumn meeting
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Sudre, L, Cheung, F, Kevorkian, L, Young, DA, Darrah, C, Donell, ST, Shepstone, L, Porter, S, Brockbank, S, Edwards, DR, Parker, AE, Clark, IM, Boubriak, OA, Urban, JPG, Cui, Z, Tew, SR, Li, Y, Tweats, LM, Hawkins, RE, Hardingham, TE, Green, D, Partridge, KA, Leveque, I, Mann, S, Oreffo, ROC, Ball, SG, Kielty, CM, Qin, M, Tai, G, Polak, JM, Bishop, AE, Stolzing, A, Scutt, A, Screen, HRC, Shelton, JC, Bader, DL, Lee, DA, Hall, A, Hayes, A, Brown, L, Tubo, R, Caterson, B, Blain, EJ, Gilbert, SJ, Duance, VC, Davies, L, Blain, E, Duance, V, Shengda, Z, Wu, M-H, Xu, X, Heywood, HK, Sims, T, Miot, S, Martin, I, Roughley, PJ, Soranzo, C, Pavesio, A, Hollander, AP, Yang, X, Webb, D, Blaker, J, Maquet, V, Boccaccini, AR, Cooper, C, Eves, P, Beck, AJ, Shard, AG, Gawkrodger, DJ, Mac Neil, S, Rajpar, MH, Kadler, KE, Thornton, DJ, Briggs, MD, Boot-Handford, RP, Ellis, MJ, Tai, C-C, Perera, S, Chaudhuri, JB, Callender, P, Mason, DJ, Colley, H, Mc Arthur, S, Mirmalek-Sani, SH, Roach, HI, Hanley, NA, Wilson, DI, MacIntosh, AC, Crawford, A, Hatton, PV, Wallis, G, Shah, R, Knowles, JC, Hunt, NP, Lewis, MP, Rippon, HJ, Ali, BE, De Bank, PA, Kellam, B, Shakesheff, KM, Comerford, EJ, Tarlton, JF, Wales, A, Bailey, AJ, Innes, JF, Olivier, V, Xie, Y, Descamps, M, Hivart, P, Lu, J, Hardouin, P, Anderson, V, Spiller, DG, Vaughan-Thomas, A, Eissa, SZS, Faram, T, Birch, HL, Zeugolis, D, Paul, G, Attenburrow, G, Bhadal, N, Whawell, SA, Worrall, LK, Rose, FRAJ, Bradshaw, TD, Stevens, MFG, Chuo, CB, Wiseman, MA, Phillips, JB, Brown, RA, Harrison, CA, Gossiel, F, Bullock, AJ, Blumsohn, A, Li, Z, Derham, B, Gaissmaier, C, Fritz, J, Krackhardt, T, Flesch, I, Aicher, WK, Ashammakhi, N, Liu, K-K, Yang, Y, Ahearne, M, Then, K, El Haj, A, Cheung, I, Wright, TC, Kostyuk, O, Baria, KE, Chowdhury, TT, Sharma, AM, Bomzon, Z, Kimmel, E, Knight, MM, Dickinson, S, Pittarello, L, Fish, RS, Ralphs, JR, Farjanel, J, Sève, S, Borel, A, Sommer, P, Hulmes, DJS, Whiting, CV, Dalton, SJ, Mitchell, DC, Kafienah, W, Mistry, S, Hollander, A, Cartmell, S, Magnay, J, Dobson, J, Appleby, RN, Salter, DM, Scutt, N, Rolf, CG, Barry, JJA, Nazhat, SN, Scotchford, CA, Howdle, SM, Roberts, S, Gargiulo, B, Evans, EH, Menage, J, Johnson, WEB, Eisenstein, S, Richardson, JB, Stenfeldt, C, Avery, NC, Tidswell, H, Crabtree, J, Frazer, A, Fraser, S, Wong, M, Beckett, K, Grobbelaar, A, Mudera, V, Bax, DV, Cain, SA, Humphries, MJ, Lomas, A, Oldershaw, R, Murdoch, A, Brennan, K, Redman, S, Haughton, L, Dowthwaite, G, Williams, A, Archer, CW, Esfandiari, E, Stokes, CR, Cox, TM, Evans, MJ, Bailey, M, Hayman, AR, Day, MJ, Williams, R, Evans, D, Adesida, A, Millwards-Sadler, J, Salter, D, Smith, R, Korda, M, Porter, R, Kalia, P, Wiseman, M, Blunn, G, Goodship, A, McClumpha, A, Horrocks, M, Pabbruwe, MB, Du, X, Stewart, K, Suciati, T, Lakey, RL, Pennington, CJ, Cawston, TE, Palmer, L, Tasman, C, Clare, M, Gidley, J, Sandy, J, Mansell, J, Ellis, T, Burger, F, Lauder, R, Khan, I, and Smith, M
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- 2005
20. Defining the role of common variation in the genomic and biological architecture of adult human height.
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Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H., Gustafsson, S., Chu, A.Y., Estrada, K., Luan, J., Kutalik, Z., Amin, N., Buchkovich, M.L., Croteau-Chonka, D.C., Day, F.R., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, A.U., Karjalainen, J., Lo, K.S., Locke, A.E., Mägi, R., Mihailov, E., Porcu, E., Randall, J.C., Scherag, A., Vinkhuyzen, A.A., Westra, H.J., Winkler, T.W., Workalemahu, T., Zhao, J.H., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, G.B., Feenstra, B., Feitosa, M.F., Fischer, K., Fraser, R.M., Goel, A., Justice, A.E., Kanoni, S., Kleber, M.E., Kristiansson, K., Lotay, V., Lui, J.C., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Nalls, M.A., Nyholt, D.R., Palmer, C.D., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, J.S., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, R.J., Sung, Y.J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S.W., van Setten, J., Van Vliet-Ostaptchouk, J.V., Wang, Z., Yengo, L., Zhang, W., Afzal, U., Arnlöv, J., Arscott, G.M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bolton, J.L., Böttcher, Y., Boyd, H.A., Buckley, B.M., Caspersen, I.H., Chines, P.S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E.W., De Jong, P.A., Deelen, J., Delgado, G., Denny, J.C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A.S., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M.E., Geller, F., Giedraitis, V., Go, A.S., Grallert, H., Grammer, T.B., Gräßler, J., Grönberg, H., de Groot, L.C., Groves, C.J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C.A., Hassinen, M., Hayward, C., Heard-Costa, N.L., Helmer, Q., Hemani, G., Henders, A.K., Hillege, H.L., Hlatky, M.A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J.J., Illig, T., Isaacs, A., James, A.L., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A.N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P.K., Mahajan, A., Maillard, M., McArdle, W.L., McKenzie, C.A., McLachlan, S., McLaren, P.J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K.L., Morken, M.A., Müller, G., Müller-Nurasyid, M., Musk, A.W., Narisu, N., Nauck, M., Nolte, I.M., Nöthen, M.M., Oozageer, L., Pilz, S., Rayner, N.W., Renstrom, F., Robertson, N.R., Rose, L.M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F.R., Scott, R.A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J.H., Smith, A.V., Smolonska, J., Stanton, A.V., Stirrups, K., Stott, D.J., Stringham, H.M., Sundström, J., Swertz, M.A., Syvänen, A.C., Tayo, B.O., Tyrer, J.P., van Dijk, S., van Schoor, N.M., van der Velde, N., van Heemst, D., van Oort, F.V., Vermeulen, S.H., Verweij, N., Vonk, J.M., Waite, L.L., Waldenberger, M., Wennauer, R., Wilkens, L.R., Willenborg, C., Wilsgaard, T., Wojczynski, M.K., Wong, A., Wright, A.F., Zhang, Q., Arveiler, D., Bakker, S.J., Beilby, J., Bergman, R.N., Bergmann, S., Biffar, R., Blangero, J., Boomsma, D.I., Bornstein, S.R., Bovet, P., Brambilla, P., Brown, M.J., Campbell, H., Caulfield, M.J., Chakravarti, A., Collins, R., Collins, F.S., Crawford, D.C., Cupples, L.A., Danesh, J., de Faire, U., den Ruijter, H.M., Erbel, R., Eriksson, J.G., Farrall, M., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, N.G., Forrester, T., Gansevoort, R.T., Gejman, P.V., Gieger, C., Golay, A., Gottesman, O., Gudnason, V., Gyllensten, U., Haas, D.W., Hall, A.S., Harris, T.B., Hattersley, A.T., Heath, A.C., Hicks, A.A., Hindorff, L.A., Hingorani, A.D., Hofman, A., Hovingh, G.K., Humphries, S.E., Hunt, S.C., Hypponen, E., Jacobs, K.B., Jarvelin, M.R., Jousilahti, P., Jula, A.M., Kaprio, J., Kastelein, J.J., Kayser, M., Kee, F., Keinanen-Kiukaanniemi, S.M., Kiemeney, L.A., Kooner, J.S., Koskinen, S., Kovacs, P., Kraja, A.T., Kumari, M., Kuusisto, J., Lakka, T.A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lupoli, S., Madden, P.A., Männistö, S., Manunta, P., Marette, A., Matise, T.C., McKnight, B., Meitinger, T., Moll, F.L., Montgomery, G.W., Morris, A.D., Morris, A.P., Murray, J.C., Nelis, M., Ohlsson, C., Oldehinkel, A.J., Ong, K.K., Ouwehand, W.H., Pasterkamp, G., Peters, A., Pramstaller, P.P., Price, J.F., Qi, L., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Rudan, I., Samani, N.J., Saramies, J., Sarzynski, M.A., Schwarz, P.E., Sebert, S., Sever, P., Shuldiner, A.R., Sinisalo, J., Steinthorsdottir, V., Stolk, R.P., Tardif, J.C., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, M.C., Amouyel, P., Asselbergs, F.W., Assimes, T.L., Bochud, M., Boehm, B.O., Bottinger, E.P., Bouchard, C., Cauchi, S., Chambers, J.C., Chanock, S.J., Cooper, R.S., de Bakker, P.I., Dedoussis, G., Ferrucci, L., Franks, P.W., Froguel, P., Groop, L.C., Haiman, C.A., Hamsten, A., Hayes, M.G., Hui, J., Hunter, D.J., Hveem, K., Jukema, J.W., Kaplan, R.C., Kivimaki, M., Kuh, D., 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Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H., Gustafsson, S., Chu, A.Y., Estrada, K., Luan, J., Kutalik, Z., Amin, N., Buchkovich, M.L., Croteau-Chonka, D.C., Day, F.R., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, A.U., Karjalainen, J., Lo, K.S., Locke, A.E., Mägi, R., Mihailov, E., Porcu, E., Randall, J.C., Scherag, A., Vinkhuyzen, A.A., Westra, H.J., Winkler, T.W., Workalemahu, T., Zhao, J.H., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, G.B., Feenstra, B., Feitosa, M.F., Fischer, K., Fraser, R.M., Goel, A., Justice, A.E., Kanoni, S., Kleber, M.E., Kristiansson, K., Lotay, V., Lui, J.C., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Nalls, M.A., Nyholt, D.R., Palmer, C.D., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, J.S., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, R.J., Sung, Y.J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S.W., van Setten, J., Van Vliet-Ostaptchouk, J.V., Wang, Z., Yengo, L., Zhang, W., Afzal, U., Arnlöv, J., Arscott, G.M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bolton, J.L., Böttcher, Y., Boyd, H.A., Buckley, B.M., Caspersen, I.H., Chines, P.S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E.W., De Jong, P.A., Deelen, J., Delgado, G., Denny, J.C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A.S., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M.E., Geller, F., Giedraitis, V., Go, A.S., Grallert, H., Grammer, T.B., Gräßler, J., Grönberg, H., de Groot, L.C., Groves, C.J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C.A., Hassinen, M., Hayward, C., Heard-Costa, N.L., Helmer, Q., Hemani, G., Henders, A.K., Hillege, H.L., Hlatky, M.A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J.J., Illig, T., Isaacs, A., James, A.L., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A.N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P.K., Mahajan, A., Maillard, M., McArdle, W.L., McKenzie, C.A., McLachlan, S., McLaren, P.J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K.L., Morken, M.A., Müller, G., Müller-Nurasyid, M., Musk, A.W., Narisu, N., Nauck, M., Nolte, I.M., Nöthen, M.M., Oozageer, L., Pilz, S., Rayner, N.W., Renstrom, F., Robertson, N.R., Rose, L.M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F.R., Scott, R.A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J.H., Smith, A.V., Smolonska, J., Stanton, A.V., Stirrups, K., Stott, D.J., Stringham, H.M., Sundström, J., Swertz, M.A., Syvänen, A.C., Tayo, B.O., Tyrer, J.P., van Dijk, S., van Schoor, N.M., van der Velde, N., van Heemst, D., van Oort, F.V., Vermeulen, S.H., Verweij, N., Vonk, J.M., Waite, L.L., Waldenberger, M., Wennauer, R., Wilkens, L.R., Willenborg, C., Wilsgaard, T., Wojczynski, M.K., Wong, A., Wright, A.F., Zhang, Q., Arveiler, D., Bakker, S.J., Beilby, J., Bergman, R.N., Bergmann, S., Biffar, R., Blangero, J., Boomsma, D.I., Bornstein, S.R., Bovet, P., Brambilla, P., Brown, M.J., Campbell, H., Caulfield, M.J., Chakravarti, A., Collins, R., Collins, F.S., Crawford, D.C., Cupples, L.A., Danesh, J., de Faire, U., den Ruijter, H.M., Erbel, R., Eriksson, J.G., Farrall, M., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, N.G., Forrester, T., Gansevoort, R.T., Gejman, P.V., Gieger, C., Golay, A., Gottesman, O., Gudnason, V., Gyllensten, U., Haas, D.W., Hall, A.S., Harris, T.B., Hattersley, A.T., Heath, A.C., Hicks, A.A., Hindorff, L.A., Hingorani, A.D., Hofman, A., Hovingh, G.K., Humphries, S.E., Hunt, S.C., Hypponen, E., Jacobs, K.B., Jarvelin, M.R., Jousilahti, P., Jula, A.M., Kaprio, J., Kastelein, J.J., Kayser, M., Kee, F., Keinanen-Kiukaanniemi, S.M., Kiemeney, L.A., Kooner, J.S., Koskinen, S., Kovacs, P., Kraja, A.T., Kumari, M., Kuusisto, J., Lakka, T.A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lupoli, S., Madden, P.A., Männistö, S., Manunta, P., Marette, A., Matise, T.C., McKnight, B., Meitinger, T., Moll, F.L., Montgomery, G.W., Morris, A.D., Morris, A.P., Murray, J.C., Nelis, M., Ohlsson, C., Oldehinkel, A.J., Ong, K.K., Ouwehand, W.H., Pasterkamp, G., Peters, A., Pramstaller, P.P., Price, J.F., Qi, L., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Rudan, I., Samani, N.J., Saramies, J., Sarzynski, M.A., Schwarz, P.E., Sebert, S., Sever, P., Shuldiner, A.R., Sinisalo, J., Steinthorsdottir, V., Stolk, R.P., Tardif, J.C., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, M.C., Amouyel, P., Asselbergs, F.W., Assimes, T.L., Bochud, M., Boehm, B.O., Bottinger, E.P., Bouchard, C., Cauchi, S., Chambers, J.C., Chanock, S.J., Cooper, R.S., de Bakker, P.I., Dedoussis, G., Ferrucci, L., Franks, P.W., Froguel, P., Groop, L.C., Haiman, C.A., Hamsten, A., Hayes, M.G., Hui, J., Hunter, D.J., Hveem, K., Jukema, J.W., Kaplan, R.C., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, N.G., März, W., Melbye, M., Moebus, S., Munroe, P.B., Njølstad, I., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Perola, M., Pérusse, L., Powell, J.E., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, P.M., Rivadeneira, F., Rotter, J.I., Saaristo, T.E., Saleheen, D., Schlessinger, D., Slagboom, P.E., Spector, T.D., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., Völzke, H., Walker, M., Wareham, N.J., Watkins, H., Wichmann, H.E., Wilson, J.F., Zanen, P., Heid, I.M., Lindgren, C.M., Mohlke, K.L., Speliotes, E.K., Barroso, I., Fox, C.S., North, K.E., Strachan, D.P., Beckmann, J.S., Berndt, S.I., Boehnke, M., Borecki, I.B., McCarthy, M.I., Metspalu, A., Uitterlinden, A.G., van Duijn, C.M., Willer, C.J., Price, A.L., Lettre, G., Loos, R.J., Weedon, M.N., Ingelsson, E., O'Connell, J.R., Abecasis, G.R., Chasman, D.I., Goddard, M.E., Visscher, P.M., Hirschhorn, J.N., and Frayling, T.M.
- Abstract
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
- Published
- 2014
21. Cell Culture in Tissue Engineering
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Hardingham, TE, primary, Kielty, CM, additional, Canfield, AE, additional, Tew, SR, additional, Ball, SG, additional, Turner, NJ, additional, and Ratcliffe, KE, additional
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22. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
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Craddock, N, Hurles, ME, Cardin, N, Pearson, RD, Plagnol, V, Robson, S, Vukcevic, D, Barnes, C, Conrad, DF, Giannoulatou, E, Holmes, C, Marchini, JL, Stirrups, K, Tobin, MD, Wain, LV, Yau, C, Aerts, J, Ahmad, T, Andrews, TD, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Clee, CM, Coffey, AJ, Connell, JMC, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Feuk, L, Fitzgerald, T, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Freathy, RM, Gibbs, P, Gilbert, P, Gokumen, O, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Onyiah, I, Ovington, NR, Owen, MJ, Palin, K, Parnell, K, Pernet, D, Perry, JRB, Phillips, A, Pinto, D, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Redon, R, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Schuilenburg, H, Scott, CE, Scott, R, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stone, MA, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Travers, ME, Turnbull, C, Valsesia, A, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Young, AH, Zeggini, E, Carter, NP, Frayling, TM, Lee, C, McVean, G, Munroe, PB, Palotie, A, Sawcer, SJ, Scherer, SW, Strachan, DP, Tyler-Smith, C, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, Donnelly, P, Craddock, N, Hurles, ME, Cardin, N, Pearson, RD, Plagnol, V, Robson, S, Vukcevic, D, Barnes, C, Conrad, DF, Giannoulatou, E, Holmes, C, Marchini, JL, Stirrups, K, Tobin, MD, Wain, LV, Yau, C, Aerts, J, Ahmad, T, Andrews, TD, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Clee, CM, Coffey, AJ, Connell, JMC, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Feuk, L, Fitzgerald, T, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Freathy, RM, Gibbs, P, Gilbert, P, Gokumen, O, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Onyiah, I, Ovington, NR, Owen, MJ, Palin, K, Parnell, K, Pernet, D, Perry, JRB, Phillips, A, Pinto, D, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Redon, R, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Schuilenburg, H, Scott, CE, Scott, R, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stone, MA, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Travers, ME, Turnbull, C, Valsesia, A, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Young, AH, Zeggini, E, Carter, NP, Frayling, TM, Lee, C, McVean, G, Munroe, PB, Palotie, A, Sawcer, SJ, Scherer, SW, Strachan, DP, Tyler-Smith, C, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, and Donnelly, P
- Abstract
Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
- Published
- 2010
23. Common polymorphisms of β 1-adrenoceptor: identification and rapid screening assay
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Maqbool, A, Hall, AS, Ball, SG, and Balmforth, AJ
- Published
- 1999
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24. Pathophysiological mechanisms of hypertensive left ventricular hypertrophy: optimising regression
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Ball, SG, primary
- Published
- 2012
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25. Hyponatraemia
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Ball, SG, primary
- Published
- 2010
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26. Beta cell differentiation during early human pancreas development
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Piper, K, primary, Brickwood, S, additional, Turnpenny, LW, additional, Cameron, IT, additional, Ball, SG, additional, Wilson, DI, additional, and Hanley, NA, additional
- Published
- 2004
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27. Partial tachyphylaxis to somatostatin (SST) analogues in a patient with acromegaly: the role of SST receptor desensitisation and circulating antibodies to SST analogues
- Author
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Wahid, ST, primary, Marbach, P, additional, Stolz, B, additional, Miller, M, additional, James, RA, additional, and Ball, SG, additional
- Published
- 2002
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28. WHAT IS THE RELEVANCE OF THE HOPE STUDY IN GENERAL PRACTICE?
- Author
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Kennedy, J, primary, Mogensen, CE, additional, Ball, SG, additional, Castaigne, AD, additional, Commerford, PJ, additional, Distiller, L, additional, Fisher, BM, additional, Gonzalez‐Jaunatey, J, additional, Nosadini, R, additional, Novials, A, additional, Östergren, J, additional, Palma‐Gámiz, J, additional, Perrone‐Filardi, P, additional, Schipperheijn, JJ, additional, Senges, J, additional, and Trevisan, R, additional
- Published
- 2001
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29. SAT0100 Fenofibrate reduces serum urate in patients with hyperuricaemia established on allopurinol
- Author
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Hepburn, AL, primary, Hogarth, MB, additional, Ball, SG, additional, Kaye, SA, additional, and Feher, MD, additional
- Published
- 2001
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30. Somatostatin Receptors: Potential Targets for Control of Cardiac Interstitial Growth
- Author
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Smith, WHT, primary, Ball, SG, additional, and Balmforth, AJ, additional
- Published
- 2000
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31. RAMIPRIL
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Smith, WHT, primary and Ball, SG, additional
- Published
- 2000
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32. The Effect of Beta-Blocker Therapy on Two Year Mortality in Patients Discharged after Myocardial Infarction with Clinical Evidence of Congestive Heart Failure
- Author
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Durham, NP, primary, Sapsford, RJ, additional, Spargias, KS, additional, Robinson, MB, additional, Greenwood, DC, additional, Jackson, BM, additional, Morrell, C, additional, Oldham, J, additional, Ball, SG, additional, and Hall, AS, additional
- Published
- 1999
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33. Common polymorphisms of β1-adrenoceptor: identification and rapid screening assay
- Author
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Maqbool, A, primary, Hall, AS, additional, Ball, SG, additional, and Balmforth, AJ, additional
- Published
- 1999
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34. PROFOUND HYPONATRAEMIA FOLLOWING AN IDIOSYNCRATIC REACTION TO DIURETICS
- Author
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WierzbiCki, AS, primary, Ball, SG, additional, and Singh, NKP, additional
- Published
- 1998
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35. 3,5-Diiodo-L-thyronine (T2) has selective thyromimetic effects in vivo and in vitro
- Author
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Ball, SG, primary, Sokolov, J, additional, and Chin, WW, additional
- Published
- 1997
- Full Text
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36. Monthly Update Cardiovascular & Renal: Update on the use of ACE-inhibition therapy after acute myocardial infarction
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Hall, As, primary and Ball, Sg, additional
- Published
- 1995
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37. Hypertensive left ventricular hypertrophy: a mechanistic approach to optimizing regression assessed by cardiovascular magnetic resonance.
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Burns J, Ball SG, Worthy G, Struthers AD, Mary DA, and Greenwood JP
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- 2012
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38. Resting sympathetic nerve activity is related to age, sex and arterial pressure but not to [alpha]2-adrenergic receptor subtype.
- Author
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Maqbool A, West RM, Galloway SL, Drinkhill MJ, Mary DA, Greenwood JP, and Ball SG
- Published
- 2010
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- View/download PDF
39. Troponin-I concentration 72 h after myocardial infarction correlates with infarct size and presence of microvascular obstruction.
- Author
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Younger JF, Plein S, Barth J, Ridgway JP, Ball SG, Greenwood JP, Younger, John F, Plein, Sven, Barth, Julian, Ridgway, John P, Ball, Stephen G, and Greenwood, John P
- Abstract
Objectives: The aim of this study was to use late gadolinium hyper-enhancement cardiac magnetic resonance (LGE-CMR) imaging to determine if a 72-h troponin-I measurement would provide a more accurate estimation of infarct size and microvascular obstruction (MVO) than serial creatine kinase (CK) or early troponin-I values.Methods: LGE-CMR was performed 3.7+/-1.4 days after medical treatment for acute ST elevation or non-ST elevation myocardial infarction. Infarct size and MVO were measured and correlated with serum troponin-I concentrations, which were sampled 12 h and 72 h after admission, in addition to serial CK levels.Results: Ninety-three patients, of whom 71 had received thrombolysis for ST elevation myocardial infarction, completed the CMR study. Peak CK, 12-h troponin-I, and 72-h troponin-I were related to infarct size by LGE-CMR (r = 0.75, p<0.0001; r = 0.56, p = 0.0003; r = 0.62, p<0.0001 respectively). Serum biomarkers demonstrated higher values in the group with MVO compared with those without MVO (Peak CK 3085+/-1531 vs 1471+/-1135, p<0.001; 12-h troponin-I 58.3+/-46.9 vs 33.4+/-40.0, p = 0.13; 72-h troponin-I 11.5+/-9.9 vs 5.5+/-4.6, p<0.005). The correlation between the extent of MVO and 12-h troponin-I was not significant (r = 0.16), in contrast to the other serum biomarkers (peak CK r = 0.44, p<0.0001; 72-h troponin-I r = 0.46, p = 0.0002).Conclusion: A single measurement of 72-h troponin-I is similar to serial CK measurements in the estimation of both myocardial infarct size and extent of MVO, and is superior to 12-h troponin-I measurements. [ABSTRACT FROM AUTHOR]- Published
- 2007
40. Safety and diagnostic accuracy of stress cardiac magnetic resonance imaging vs exercise tolerance testing early after acute ST elevation myocardial infarction.
- Author
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Greenwood JP, Younger JF, Ridgway JP, Sivananthan MU, Ball SG, and Plein S
- Abstract
OBJECTIVE: To determine the safety and diagnostic accuracy of adenosine-stress cardiac magnetic resonance (CMR) perfusion imaging early after acute ST elevation myocardial infarction (STEMI) compared with standard exercise tolerance testing (ETT). DESIGN AND SETTING: Cross sectional observational study in a university teaching hospital. PATIENTS: 35 patients admitted with first acute STEMI. INTERVENTIONS: All patients underwent a CMR imaging protocol which included rest and adenosine-stress perfusion, viability, and cardiac functional assessment. All patients also had an ETT (modified Bruce protocol) and x ray coronary angiography. MAIN OUTCOME MEASURES: Safety and diagnostic accuracy of adenosine-stress perfusion CMR vs ETT early after STEMI in identifying patients with significant coronary stenosis (>or=70%) and the need for coronary revascularisation. Also, to determine if CMR can distinguish between ischaemia in the peri-infarct zone and ischaemia in remote myocardium. RESULTS: CMR imaging was well tolerated (all patients completed the protocol) and no complications occurred. CMR was more sensitive (86% vs 48%, p = 0.0074) and more specific than ETT (100% vs 50%, p<0.0001) for detecting significant coronary stenosis, and more sensitive for predicting revascularisation (94% vs 56%, p = 0.039). Inducible ischaemia in the infarct related artery territory was seen in 21 of 35 patients and was associated with smaller infarct size and less transmurality of infarction. CONCLUSIONS: Adenosine-stress CMR imaging is safe early after acute STEMI and identifies patients with significant coronary stenosis more accurately than ETT. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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41. Relationship between central sympathetic drive and magnetic resonance imaging-determined left ventricular mass in essential hypertension.
- Author
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Burns J, Sivananthan MU, Ball SG, Mackintosh AF, Mary DA, Greenwood JP, Burns, Joanna, Sivananthan, Mohan U, Ball, Stephen G, Mackintosh, Alan F, Mary, David A S G, and Greenwood, John P
- Published
- 2007
42. The Effect Angiotensin Converting Enzyme Inhibition (ACEI) on Efferent Cardiac Vagal Nerve Responses to Stimulation of Carotid Sinus Baroreceptors
- Author
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Patel, PK, primary, Ball, SG, additional, and Mary, Dasg, additional
- Published
- 1990
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43. beta blocker treatment and other prognostic variables in patients with clinical evidence of heart failure after acute myocardial infarction: evidence from the AIRE study.
- Author
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Spargias KS, Hall AS, Greenwood DC, Ball SG, Spargias, K S, Hall, A S, Greenwood, D C, and Ball, S G
- Abstract
Objectives: To examine clinical outcomes associated with optional beta blockade in a population of patients with evidence of heart failure after myocardial infarction.Design and Patients: Data from the acute infarction ramipril efficacy (AIRE) study were analysed retrospectively. At baseline 22.3% of the patients were receiving a beta blocker. To minimise confounding, beta blocker and diuretic treatments, presence of clinical signs of heart failure, left ventricular ejection fraction, and 16 other baseline clinical variables were simultaneously entered in a multivariate Cox regression model. In addition, the same analysis was repeated separately within a high and a low risk group of patients, as defined according to the need for diuretic treatment.Results: beta Blocker treatment was an independent predictor of reduced risk of total mortality (hazard ratio 0.66, 95% confidence interval (CI) 0. 48 to 0.90) and progression to severe heart failure (0.58, 95% CI 0.40 to 0.83) for the entire study population. There were similar findings in high risk patients requiring diuretics (0.59, 95% CI 0.40 to 0.86; and 0.58, 95% CI 0.38 to 0.89).Conclusions: beta Blocker treatment is associated with improved outcomes in patients with clinical evidence of mild to moderate heart failure after myocardial infarction. Most importantly, high risk patients with persistent heart failure appear to benefit at least as much as lower risk patients with transient heart failure. [ABSTRACT FROM AUTHOR]- Published
- 1999
44. A dose-response study of HOE 498, a new non-sulphydryl converting enzyme inhibitor, on blood pressure, pulse rate and the renin- angiotensin-aldosterone system in normal man.
- Author
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Manhem, PJ, Ball, SG, Morton, JJ, Murray, GD, Leckie, BJ, Fraser, R, and Robertson, JI
- Abstract
The effect of different oral doses of HOE 498, a new non-sulphydryl containing converting enzyme inhibitor, was investigated in a double- blind, placebo-controlled study in normotensive volunteers. Dose- related reductions in serum converting enzyme activity, plasma angiotensin II and aldosterone were seen, greater at 4 h than at 12 h after drug ingestion. Converse dose-related increases in blood angiotensin I and plasma active renin concentration occurred. Falls of angiotensin II were as great with 20 mg as with 50 mg of HOE 498, although the effect was more prolonged with 50 mg. The reductions in concentrations of plasma angiotensin II and serum converting enzyme activity and the increases in plasma renin concentration were correlated with the concentration of HOE 498 - diacid in plasma. Dose- related falls in both supine and erect blood pressure were maximal 2- 3.5 h after dosing. Pulse rate increased marginally but insignificantly in the supine; slightly and significantly in the upright position, concomitantly with the blood pressure reduction at all doses of active drug. We conclude that effects of single doses of HOE 498 on the renin- angiotensin system are maximal within 4 h, but are still apparent after 24 h. Thus it is likely that once daily administration will be adequate for treatment of high blood pressure in patients. [ABSTRACT FROM AUTHOR]
- Published
- 1985
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- View/download PDF
45. Effect of the 5-hydroxytryptamine type 2 receptor antagonist, ketanserin, on blood pressure, the renin-angiotensin system and sympatho-adrenal function in patients with essential hypertension.
- Author
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Zabludowski, JR, Zoccali, C, Isles, CG, Murray, GD, Robertson, JI, Inglis, GC, Fraser, R, and Ball, SG
- Abstract
Ketanserin, a 5-HT type 2 receptor antagonist, was administered intravenously to nine patients with essential hypertension in a double- blind placebo controlled study to investigate the drug's effects on blood pressure, heart rate, the renin-angiotensin system and sympatho- adrenal function. Average blood-pressure for the group prior to injection of the drug was 150 +/- 7/94 +/- 4 (s.e. mean) mm Hg and decreased significantly (P less than 0.01) to 137 +/- 8/88 +/- 5 mm Hg during the 2 h after injection; heart rate increased immediately after injection of ketanserin, reaching a maximum of 81 +/- 4 beats/min. After drug administration systolic and diastolic blood pressure decreased on tilting, but the heart rate response was not different from that with placebo. Ketanserin did not affect the blood pressure response to graded infusion of the alpha 1-adrenoceptor agonist phenylephrine. Plasma active renin, angiotensin II and aldosterone concentrations increased slightly but not significantly after the drug; plasma noradrenaline increased transiently. 5-HT may be important in the maintenance of blood pressure but alternative mechanisms for the action of ketanserin in reducing blood pressure require investigation. [ABSTRACT FROM AUTHOR]
- Published
- 1984
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46. The effect of a 5-HT antagonist, ketanserin, on blood pressure, the renin-angiotensin system and sympathoadrenal function in normal man.
- Author
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Zoccali, C, Zabludowski, JR, Isles, CG, Murray, GD, Inglis, GC, Robertson, JI, Fraser, R, and Ball, SG
- Abstract
The role of endogenous 5-hydroxytryptamine (5-HT) in the control of blood pressure, the renin-angiotensin system and sympatho-adrenal function was investigated in normal man. Ketanserin (a specific 5-HT2 antagonist) administered intravenously caused a small decrease in blood pressure in salt-depleted recumbent subjects. A more marked postural fall in pressure occurred in both sodium-depleted and repleted normal subjects. Plasma active renin concentration and angiotensin II increased after administration of ketanserin, but plasma aldosterone, cortisol and noradrenaline were unchanged. 5-HT may be important in the control of blood pressure in man and specific 5-HT2 receptor antagonists could be a useful new class of antihypertensive agents. [ABSTRACT FROM AUTHOR]
- Published
- 1983
- Full Text
- View/download PDF
47. Converting Enzyme Inhibitors and the Cardiovascular System
- Author
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Ball Sg
- Subjects
Pharmacology ,chemistry.chemical_classification ,medicine.medical_specialty ,business.industry ,Hemodynamics ,Angiotensin-Converting Enzyme Inhibitors ,Blood flow ,medicine.disease ,Cardiovascular System ,Compliance (physiology) ,Enzyme ,Blood pressure ,chemistry ,Cardiovascular Diseases ,Internal medicine ,Cardiac hypertrophy ,medicine ,Cardiology ,Humans ,Ischaemic heart disease ,Cardiology and Cardiovascular Medicine ,business ,Beneficial effects ,Stroke - Abstract
Most commonly used drugs reduce blood pressure equally. Reduction in pressure lessens the chance of stroke but appears to have little impact on death from ischaemic heart disease in the majority. Loss of arterial compliance, development of cardiac hypertrophy, impaired coronary blood flow, and dysrhythmias may contribute, at least in part, to the adverse cardiac effects of hypertension. It is speculated that converting enzyme inhibitors could offer beneficial effects in these areas.
- Published
- 1987
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48. Cultured mesenteric vascular smooth muscle cells express dopamine DA1-receptors
- Author
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Lyall F, Ball Sg, Balmforth Aj, and Morton Ji
- Subjects
medicine.medical_specialty ,Vascular smooth muscle ,Dopamine ,Adenylate kinase ,Vasodilation ,Cyclase ,Muscle, Smooth, Vascular ,Receptors, Dopamine ,Internal medicine ,medicine ,Cyclic AMP ,Animals ,Receptor ,Mesenteric arteries ,Cells, Cultured ,Pharmacology ,Chemistry ,Benzazepines ,Propranolol ,Mesenteric Arteries ,Endocrinology ,medicine.anatomical_structure ,Dopamine receptor ,medicine.drug ,Adenylyl Cyclases - Abstract
Incubation of cultured mesenteric vascular smooth muscle cells with dopamine, in the presence of propranolol, caused an increase in cyclic AMP formation in a concentration-dependent manner (Ka apparent 6.8 +/- 0.5 microM). This effect of dopamine was inhibited by the DA1-receptor antagonist SCH 23390 (Ki = 1 nM). These results suggest that cultured mesenteric vascular smooth muscle cells express DA1-receptors linked to adenylate cyclase.
- Published
- 1988
49. Genome-wide association study identifies eight loci associated with blood pressure
- Author
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Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K, Nilsson, P, Van Der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliot, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, De Jong, PE, Snieder, H, Van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Altshuler, D, Jarvelin, M, Elliott, P, Lakatta, EG, Forouhi, N, Wareham, NJ, Loos, RJF, Deloukas, P, Lathrop, GM, Zelenika, D, Strachan, DP, Soranzo, N, Williams, FM, Zhai, G, Spector, TD, Peden, JF, Watkins, H, Ferrucci, L, Caulfield, M, Munroe, PB, Berglund, G, Melander, O, Matullo, G, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Ernst, F, Homuth, G, Völker, U, Elosua, R, Laakso, M, Connell, JM, Mooser, V, Salomaa, V, Tuomilehto, J, Laan, M, Navis, G, Seedorf, U, Syvänen, A, Tognoni, G, Sanna, S, Uda, M, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Felix, SB, Reffelmann, T, Lorbeer, R, Völzke, H, Rettig, R, Galan, P, Hercberg, S, Bingham, SA, Kooner, JS, Bandinelli, S, Meneton, P, Abecasis, G, Thompson, JR, Braga Marcano, CA, Barke, B, Dobson, R, Gungadoo, J, Lee, KL, Onipinla, A, Wallace, I, Xue, M, Clayton, DG, Leung, H, Nutland, S, Walker, NM, Todd, JA, Stevens, HE, Dunger, DB, Widmer, B, Downes, K, Cardon, LR, Kwiatkowski, DP, Barrett, JC, Evans, D, Morris, AP, Lindgren, CM, Rayner, NW, Timpson, NJ, Lyons, E, Vannberg, F, Hill, AVS, Teo, YY, Rockett, KA, Craddock, N, Attwood, AP, Bryan, C, Bumpstead, SJ, Chaney, A, Ghori, J, William, RG, Hunt, SE, Inouye, M, Keniry, E, King, E, McGinnis, R, Potter, S, Ravindrarajan, R, Whittaker, P, Withers, D, Bentley, D, Groves, CJ, Duncanson, A, Ouwehand, WH, Boorman, JP, Cant, B, Jolley, JD, Knight, AS, Koch, K, Taylor, NC, Watkins, NA, Winzer, T, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Donnely, P, Davidson, D, Marchini, JL, Spencer, ICA, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, IB, Howie, BN, Su, Z, Vukcevic, D, Easton, D, Everson, U, Hussey, JM, Meech, E, Prowse, CV, Walters, GR, Jones, RW, Ring, SM, Prembey, M, Breen, G, St Clair, D, Ceasar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskovina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGruffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, DT, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Lewis, CM, Onnie, CM, Prescott, NJ, Mathew, CG, Forbes, A, Sanderson, J, Mathew, C, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hider, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DPM, Thomson, W, Worthington, J, Frayling, TM, Freathy, RM, Lango, H, Perry, JRB, Weedon, MN, Hattersley, AT, Shields, BM, Hitman, GA, Walker, M, Newport, M, Sirugo, G, Conway, D, Jallow, M, Bradbury, LA, Pointon, JL, Brown, MA, Farrar, C, Wordsworth, P, Franklyn, JA, Heward, JM, Simmonds, MJ, Cough, SCL, Seal, S, Stratton, MR, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K, Nilsson, P, Van Der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliot, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, De Jong, PE, Snieder, H, Van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Altshuler, D, Jarvelin, M, Elliott, P, Lakatta, EG, Forouhi, N, Wareham, NJ, Loos, RJF, Deloukas, P, Lathrop, GM, Zelenika, D, Strachan, DP, Soranzo, N, Williams, FM, Zhai, G, Spector, TD, Peden, JF, Watkins, H, Ferrucci, L, Caulfield, M, Munroe, PB, Berglund, G, Melander, O, Matullo, G, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Ernst, F, Homuth, G, Völker, U, Elosua, R, Laakso, M, Connell, JM, Mooser, V, Salomaa, V, Tuomilehto, J, Laan, M, Navis, G, Seedorf, U, Syvänen, A, Tognoni, G, Sanna, S, Uda, M, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Felix, SB, Reffelmann, T, Lorbeer, R, Völzke, H, Rettig, R, Galan, P, Hercberg, S, Bingham, SA, Kooner, JS, Bandinelli, S, Meneton, P, Abecasis, G, Thompson, JR, Braga Marcano, CA, Barke, B, Dobson, R, Gungadoo, J, Lee, KL, Onipinla, A, Wallace, I, Xue, M, Clayton, DG, Leung, H, Nutland, S, Walker, NM, Todd, JA, Stevens, HE, Dunger, DB, Widmer, B, Downes, K, Cardon, LR, Kwiatkowski, DP, Barrett, JC, Evans, D, Morris, AP, Lindgren, CM, Rayner, NW, Timpson, NJ, Lyons, E, Vannberg, F, Hill, AVS, Teo, YY, Rockett, KA, Craddock, N, Attwood, AP, Bryan, C, Bumpstead, SJ, Chaney, A, Ghori, J, William, RG, Hunt, SE, Inouye, M, Keniry, E, King, E, McGinnis, R, Potter, S, Ravindrarajan, R, Whittaker, P, Withers, D, Bentley, D, Groves, CJ, Duncanson, A, Ouwehand, WH, Boorman, JP, Cant, B, Jolley, JD, Knight, AS, Koch, K, Taylor, NC, Watkins, NA, Winzer, T, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Donnely, P, Davidson, D, Marchini, JL, Spencer, ICA, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, IB, Howie, BN, Su, Z, Vukcevic, D, Easton, D, Everson, U, Hussey, JM, Meech, E, Prowse, CV, Walters, GR, Jones, RW, Ring, SM, Prembey, M, Breen, G, St Clair, D, Ceasar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskovina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGruffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, DT, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Lewis, CM, Onnie, CM, Prescott, NJ, Mathew, CG, Forbes, A, Sanderson, J, Mathew, C, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hider, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DPM, Thomson, W, Worthington, J, Frayling, TM, Freathy, RM, Lango, H, Perry, JRB, Weedon, MN, Hattersley, AT, Shields, BM, Hitman, GA, Walker, M, Newport, M, Sirugo, G, Conway, D, Jallow, M, Bradbury, LA, Pointon, JL, Brown, MA, Farrar, C, Wordsworth, P, Franklyn, JA, Heward, JM, Simmonds, MJ, Cough, SCL, Seal, S, Stratton, MR, Ban, M, Goris, A, Sawcer, SJ, and Compston, A
- Abstract
Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10−24), CYP1A2 (P = 1 × 10−23), FGF5 (P = 1 × 10−21), SH2B3 (P = 3 × 10−18), MTHFR (P = 2 × 10−13), c10orf107 (P = 1 × 10−9), ZNF652 (P = 5 × 10−9) and PLCD3 (P = 1 × 10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
50. The effect of carbidopa administration on urinary sodium excretion in man. Is dopamine an intrarenal natriuretic hormone?
- Author
-
Ball, SG, primary and Lee, MR, additional
- Published
- 1977
- Full Text
- View/download PDF
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