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1. Oxidative stress and free radicals in COPD – implications and relevance for treatment

Author

Domej W, Oettl K, and Renner W

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Wolfgang Domej,1 Karl Oettl,2 Wilfried Renner31Division of Pulmonology, Department of Internal Medicine, 2Institute of Physiological Chemistry, 3Clinical Institute of Medical and Chemical Diagnostics, Medical University of Graz, Graz, AustriaAbstract: Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD). In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells. This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options. Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD. Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases. In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented.Keywords: reactive oxygen species, reactive nitrogen species, chronic obstructive pulmonary disease, antioxidants

Published
2014

2. CYP2D6 Genotype and Adjuvant Tamoxifen: Meta‐Analysis of Heterogeneous Study Populations

Author

Province, MA, Goetz, MP, Brauch, H, Flockhart, DA, Hebert, JM, Whaley, R, Suman, VJ, Schroth, W, Winter, S, Zembutsu, H, Mushiroda, T, Newman, WG, Lee, M‐T M, Ambrosone, CB, Beckmann, MW, Choi, J‐Y, Dieudonné, A‐S, Fasching, PA, Ferraldeschi, R, Gong, L, Haschke‐Becher, E, Howell, A, Jordan, LB, Hamann, U, Kiyotani, K, Krippl, P, Lambrechts, D, Latif, A, Langsenlehner, U, Lorizio, W, Neven, P, Nguyen, AT, Park, B‐W, Purdie, CA, Quinlan, P, Renner, W, Schmidt, M, Schwab, M, Shin, J‐G, Stingl, JC, Wegman, P, Wingren, S, Wu, AHB, Ziv, E, Zirpoli, G, Thompson, AM, Jordan, VC, Nakamura, Y, Altman, RB, Ames, MM, Weinshilboum, RM, Eichelbaum, M, Ingle, JN, Klein, TE, and Consortium, International Tamoxifen Pharmacogenomics

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Breast Cancer, Women's Health, Estrogen, Aging, Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Antineoplastic Agents, Hormonal, Breast Neoplasms, Cytochrome P-450 CYP2D6, Female, Genetic Variation, Genotype, Humans, Menopause, Middle Aged, Pharmacogenetics, Survival Analysis, Tamoxifen, Treatment Outcome, International Tamoxifen Pharmacogenomics Consortium, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.

Published
2014

11. Expression of genes kdsA and kdsB involved in 3-deoxy-D-manno-octulosonic acid metabolism and biosynthesis of enterobacterial lipopolysaccharide is growth phase regulated primarily at the transcriptional level in Escherichia coli K-12

Author

Strohmaier, H., Remler, P., Renner, W., and Hogenauer, G.

Subjects
Enterobacteriaceae -- Research, Biosynthesis -- Analysis, Escherichia coli -- Research, Biological sciences
Abstract

Escherichia coli K-12's kdsA and kdsB gene expression is regulated by growth phase at the transcriptional level and so stops expression once the stationary cell phase begins. kdsA's product catalyzes 3-deoxy-D-manno-octulosonic acid and kdsB's product activates it. The exact regulation mechanism is unknown but probably involves trans- and cis-acting factors. The persistence of these genes' products is probably due to their stability and non-protease degradability.

Published
1995

13. Training of emotional intelligence in depressive inpatients

Author

Muhlberger M. Muhlberger and Renner W. Renner

Subjects
Social support, business.industry, Emotional intelligence, Injury prevention, Medicine, Major depressive disorder, Human factors and ergonomics, Poison control, business, medicine.disease, Suicide prevention, Occupational safety and health, Clinical psychology
Abstract

Deficits in emotional intelligence are possible factors in provoking and maintaining depressive symptoms in patients with major depressive disorder. Aim of the present study was to explore the effects of a training of emotional intelligence based on the model of Salovey and Mayer on emotional competencies and depressive symptoms in depressive inpatients over six weeks (tpost) and twelve months (tfollow-up). 171 depressive inpatients (men = 67, women = 104) were randomly assigned to either a training of emotional intelligence together with treatment as usual (TAU) or TAU alone. Participants of the training group showed significant positive changes in their emotional competencies after six weeks of therapy (Cohens d = 0.43-0.49); in contrast, they showed no differences in depressive symptomatology compared to the control group. In the follow-up,the patients of the control group declined significantly in their depressive symptoms while the training group maintained or even improved. The acquired emotional competencies may facilitate the use of adaptive coping strategies as well as of social support in stressful situations. In conclusion, this training of emotional intelligence enhances emotional competencies, in the long term it may prevent relapse in depressive episodes. Language: en

Published
2016

14. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author

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. 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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, and Kooner, Js.

Subjects
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.

Published
2016

15. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author

Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'an, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, 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. 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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.

Subjects
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

Published
2011

16. Adopting basic principles of the United Nations Academic Impact initiative (UNAI): Can cultural differences be predicted from value orientations and globalization?

Author

Nechtelberger, A, Renner, W, Nechtelberger, M, Supeková, SC, Hadjimarkou, M, Offurum, C, Ramalingam, P, Senft, B, Redfern, K, Nechtelberger, A, Renner, W, Nechtelberger, M, Supeková, SC, Hadjimarkou, M, Offurum, C, Ramalingam, P, Senft, B, and Redfern, K

Abstract

© 2017 Nechtelberger, Renner, Nechtelberger, Supeková, Hadjimarkou, Offurum, Ramalingam, Senft and Redfern. The United Nations Academic Impact (UNAI) Initiative has set forth 10 Basic Principles for higher education. In the present study, a 10 item self-report questionnaire measuring personal endorsement of these principles has been tested by self-report questionnaires with university and post-graduate students from Austria, China, Cyprus, India, Nigeria, and Slovakia (total N = 976, N = 627 female, mean age 24.7 years, s = 5.7). Starting from the assumptions of Moral Foundations Theory (MFT), we expected that personal attitudes toward the UNAI Basic Principles would be predicted by endorsement of various moral foundations as suggested by MFT and by the individual's degree of globalization. Whereas for the Austrian, Cypriot, and Nigerian sub- samples this assumption was largely confirmed, for the Chinese, Indian, and Slovak sub- samples only small amounts of the variance could be explained by regression models. All six sub-samples differed substantially with regard to their overall questionnaire responses: by five discriminant functions 83.6% of participants were classified correctly. We conclude that implementation of UNAI principles should adhere closely to the cultural requirements of the respective society and, where necessary should be accompanied by thorough informational campaigns about UN educational goals.

Published
2017

17. The psycho-lexical approach in exploring the field of values: A reply to Schwartz

Author

Universitat Rovira i Virgili, Raad B, Timmerman ME, Morales-Vives F, Renner W, Barelds DPH, Pieter Van Oudenhoven J, Universitat Rovira i Virgili, and Raad B, Timmerman ME, Morales-Vives F, Renner W, Barelds DPH, Pieter Van Oudenhoven J

Abstract

We reply to each of the issues raised by Schwartz in a commentary on our article on a comparison of value taxonomies. We discuss two approaches, mentioned in that commentary, the lexical approach and the theory-driven approach, especially with respect to their capacities in covering the domain of values and with respect to the representation of important values in a useful structure. We refute the critique by Schwartz that the lexical approach is superfluous, because his theory "toward universals in values" would already cover all values, and that their mutual relationships are relevant to individuals around the globe. We explain the necessity and strength of the lexical approach in taxonomizing the value domain, both within and across languages. Furthermore, we argue that principal components analysis (PCA) and simultaneous component analysis (SCA) are most adequate in arriving at a satisfactory structuring of the great many values in terms of both underlying constructs and their facets. We point to a misrepresentation in Schwartz's circular model, and we review some misunderstandings on the side of Schwartz with respect to our results in comparison with those proceeding from his circular model.

Published
2017

24. Intensity-dependent stimulation of leukocyte telomerase activity by endurance exercise – a pilot study

Author

Niedrist Tobias, Pailer Sabine, Jahrbacher Renate, Gruber Hans-Jürgen, Herrmann Markus, and Renner Wilfried

Subjects
cellular senescence, physical exercise, shelterins, telomerase, telomeres, Medical technology, R855-855.5
Abstract

Exercise induces telomerase activity and regulates shelterin expression. These effects are believed to preserve telomeres. However, the impact of exercise intensity on telomerase and shelterins has not been studied systematically. This pilot study investigated the kinetics of leukocyte telomerase activity (LTA) and the expression of telomere-related genes in response to exercise at different intensities.

Published
2022
Full Text
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25. Large scale association analysis of novel genetic loci for coronary artery disease

Author

Amouyel, P., Arveiler, D., Boekholdt, S. M., Braund, P., Bruse, P., Bumpstead, S. J., Bugert, P., Cambien, F., Danesh, J., Deloukas, P., Doering, A., Ducimetiere, P., Dunn, R. M., El Mokhtari, N. E., Erdmann, J., Evans, A., Ewels, P., Ferrieres, J., Fischer, Matthias, Frossard, P., Garner, S., Gieger, C., Gohri, M. J. R., Goodall, A. H., Grosshennig, A., Hall, A., Hardwick, R., Haukijarvi, A., Hengstenberg, C., Illig, T., Karvanen, J., Kastelein, J., Kee, F., Khaw, K. T., Kluter, H., Konig, I. R., Kuulasmaa, K., Laiho, P., Luc, G., Marz, W., McGinnis, R., McLaren, W., Meisinger, C., Morrison, C., Ou, X., Ouwehand, W. H., Preuss, M., Proust, C., Ravindrarajah, R., Renner, W., Rice, K., Ruidavets, J. B., Saleheen, D., Salomaa, V., Samani, N. J., Sandhu, M. S., Schafer, A. S., Scholz, M., Schreiber, Stefan, Schunkert, H., Silander, K., Singh, R., Soranzo, N., Stark, K., Stegmayr, B., Stephens, J., Thompson, J., Tiret, L., Trip, M. D., van der Schoot, E., Virtamo, J., Wareham, N. J., Wichmann, H. E., Wiklund, P. G., Wright, B., Ziegler, A., Zwaginga, J. J., Amsterdam Cardiovascular Sciences, and Cardiology

Subjects
Male, Risk, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, Coronary Artery Disease, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, White People, Article, Coronary artery disease, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Odds Ratio, medicine, Humans, Genetic Predisposition to Disease, Family history, Aged, 030304 developmental biology, Genetic association, Genetics, 0303 health sciences, business.industry, Case-control study, Odds ratio, Middle Aged, medicine.disease, Case-Control Studies, Female, business, Cardiology and Cardiovascular Medicine, Genome-Wide Association Study
Abstract

Background— Combined analysis of 2 genome-wide association studies in cases enriched for family history recently identified 7 loci (on 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21, 10q11.21, and 15q22.33) that may affect risk of coronary artery disease (CAD). Apart from the 9p21 locus, the other loci await substantive replication. Furthermore, the effect of these loci on CAD risk in a broader range of individuals remains to be determined. Methods and Results— We undertook association analysis of single nucleotide polymorphisms at each locus with CAD risk in 11 550 cases and 11 205 controls from 9 European studies. The 9p21.3 locus showed unequivocal association (rs1333049, combined odds ratio [OR]=1.20, 95% CI [1.16 to 1.25], probability value=2.81×10 −21 ). We also confirmed association signals at 1p13.3 (rs599839, OR=1.13 [1.08 to 1.19], P =1.44×10 −7 ), 1q41 (rs3008621, OR=1.10 [1.04 to 1.17], P =1.02×10 −3 ), and 10q11.21 (rs501120, OR=1.11 [1.05 to 1.18], P =4.34×10 −4 ). The associations with 6q25.1 (rs6922269, P =0.020) and 2q36.3 (rs2943634, P =0.032) were borderline and not statistically significant after correction for multiple testing. The 15q22.33 locus did not replicate. The 10q11.21 locus showed a possible sex interaction ( P =0.015), with a significant effect in women (OR=1.29 [1.15 to 1.45], P =1.86×10 −5 ) but not men (OR=1.03 [0.96 to 1.11], P =0.387). There were no other strong interactions of any of the loci with other traditional risk factors. The loci at 9p21, 1p13.3, 2q36.3, and 10q11.21 acted independently and cumulatively increased CAD risk by 15% (12% to 18%), per additional risk allele. Conclusions The findings provide strong evidence for association between at least 4 genetic loci and CAD risk. Cumulatively, these novel loci have a significant impact on risk of CAD at least in European populations.

Published
2009

26. The association between common vitamin D receptor gene variations and osteoporosis

Author

Uitterlinden, A. G., Ralston, S. H., Brandi, M. L., Carey, A. H., Grinberg, D., Langdahl, B. L., Lips, P., Lorenc, R., Obermayer-Pietsxch, B., Reeve, J., Reid, D. M., Amedei, A., Bassiti, A., Bustamante, M., Husted, L. B., Diez-Perez, A., Dobnig, H., Dunning, A. M., Enjuanes, A., Fahrleitner-Pammer, A., Fang, Y., Karczmarewicz, E., Kruk, M., Johannes van Leeuwen, Mavilia, C., Meurs, J. B. J., Mangion, J., Mcguigan, F. E. A., Pols, H. A. P., Renner, W., Rivadeneira, F., Schoor, N. M., Scollen, S., Sherlock, R. E., Ioannidis, J. P. A., Parsons, C., Bear, S., Farmer, R., Lukaszkiewicz, J., Bilinski, P., Czerwinski, E., Lewinski, A., Marcinowska-Suchowierska, E., Milewicz, A., Spaczynski, M., Jaworski, M., Nuti, R., Grazio, S., Miazgowski, T., Boonen, R., Masaryk, P., Stepan, J. J., Lopes Vaz, A., Cannata, J., Weber, K., Benevolenskaya, L. I., Todd, C., Khaw, K. -T, Da Silva, J., Bhalla, A., Poor, G., Bruges Armas, J., Lyritis, G., O Neill, T. W., Lunt, M., Compston, J., Cooper, C., Duncan, E., Keen, R., Mclellan, A., Wass, J., Dekema, E., Essen, H., Pluijm, S., Bravenboer, N., Hofman, A., Duijn, C. M., Jong, P. J., Breteler, M. M., Stricker, B. H., Witteman, J. C., Internal medicine, VU University medical center, and Internal Medicine

Subjects
Male, Bone density, Osteoporosis, Osteoporosis/*genetics, Fractures, Bone/genetics, Calcitriol receptor, Fractures, Bone, chemistry.chemical_compound, Bone Density, Receptors, Calcitriol/*genetics, CDX2 Transcription Factor, Prospective Studies, Deoxyribonucleases, Type II Site-Specific, Promoter Regions, Genetic, education.field_of_study, biology, General Medicine, Middle Aged, FokI, Vitamin D3 Receptor, Female, musculoskeletal diseases, Adult, Bone Density/*genetics, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, TaqI, Genotype, Population, Polymorphism, Genetic, Homeodomain Proteins/*genetics, Internal medicine, Internal Medicine, medicine, Vitamin D and neurology, Humans, education, Aged, Homeodomain Proteins, business.industry, medicine.disease, Endocrinology, chemistry, Haplotypes, biology.protein, Receptors, Calcitriol, business
Abstract

Background: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. Objective: To evaluate the relation between VDR polymorphisms, BMD, and fractures. Design: Prospective multicenter large-scale association study. Setting: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. Participants: 26 242 participants (18 405 women). Measurements: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. Results: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). Limitations: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. Conclusions: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.

Published
2006

27. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Author

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., 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., 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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

28. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Li, M., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Li, Y., 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., Abecasis, G.R., Adair, L.S., Alexander, M., Altshuler, D., Amin, N., Arking, D.E., Arora, P., Aulchenko, Y., Bakker, S.J.L., Bandinelli, S., Barroso, I., Beckmann, J.S., Beilby, J.P., Bergman, R.N., Bergmann, S., Bis, J.C., Boehnke, M., Bonnycastle, L.L., Bornstein, S.R., Bots, M.L., Bragg-Gresham, J.L., Brand, S.-M., Brand, E., Braund, P.S., Brown, M.J., Burton, P.R., Casas, J.P., Caulfield, M.J., Chakravarti, A., Chambers, J.C., Chandak, G.R., Chang, Y.-P.C., Charchar, F.J., Chaturvedi, N., Cho, Y.S., Clarke, R., Collins, F.S., Collins, R., Connell, J.M., Cooper, J.A., Cooper, M.N., Cooper, R.S., Corsi, A.M., Dörr, M., Dahgam, S., Danesh, J., Smith, G.D., Day, I.N.M., Deloukas, P., Denniff, M., Dominiczak, A.F., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, F.G.R., Fox, E.R., Frayling, T.M., Galan, P., Ganesh, S.K., Garcia, M., Gaunt, T.R., Glazer, N.L., Go, M.J., Goel, A., Grässler, J., Grobbee, D.E., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, B.-G., Hardy, R., Hartikainen, A.-L., Heath, S., Heckbert, S.R., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, A.A., Hilton, G., Hingorani, A.D., Hoffman Bolton, J.A., Hopewell, J.C., Howard, P., Humphries, S.E., Hunt, S.C., Hveem, K., Ikram, M.A., Islam, M., Iwai, N., Jarvelin, M.-R., Jackson, A.U., Jafar, T.H., Janipalli, C.S., Johnson, T., Kathiresan, S., Khaw, K.-T., Kim, H.-L., Kinra, S., Kita, Y., Kivimaki, M., Kooner, J.S., Kumar, M.J.K., Kuh, D., Kulkarni, S.R., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, E.G., Langefeld, C.D., Larson, M.G., Lathrop, M., Lawlor, D.A., Lawrence, R.W., Lee, J.-Y., Lee, N.R., Levy, D., Longstreth, W.T., Luan, J., Lucas, G., Ludwig, B., Mangino, M., Mani, K.R., Marmot, M.G., Mattace-Raso, F.U.S., Matullo, G., McArdle, W.L., McKenzie, C.A., Meitinger, T., Melander, O., Meneton, P., Meschia, J.F., Miki, T., Milaneschi, Y., Mohlke, K.L., Mooser, V., Morken, M.A., Morris, R.W., Mosley, T.H., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, K.-D.H., Nilsson, P., Nyberg, F., O'Donnell, C.J., Ogihara, T., Ohkubo, T., Okamura, T., Ong, R.T.-H., Ongen, H., Onland-Moret, N.C., O'Reilly, P.F., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, L.J., Palmer, N.D., Parker, A.N., Peden, J.F., Peltonen, L., Perola, M., Pihur, V., Platou, C.G.P., Plump, A., Prabhakaran, D., Psaty, B.M., Raffel, L.J., Rao, D.C., Rasheed, A., Ricceri, F., Rice, K.M., Rosengren, A., Rotter, J.I., Rudock, M.E., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, N.J., Schwartz, S.M., Schwarz, P.E.H., Scott, L.J., Scott, J., Scuteri, A., Sehmi, J.S., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, N.R.G., Sijbrands, E.J.G., Sim, X., Singleton, A., Sjögren, M., Smith, N.L., Artigas, M.S., Spector, T.D., Staessen, J.A., Stancakova, A., Steinle, N.I., Strachan, D.P., Stringham, H.M., Sun, Y.V., Swift, A.J., Tabara, Y., Tai, E.-S., Talmud, P.J., Taylor, A., Terzic, J., Thelle, D.S., Tobin, M.D., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, C.S.P.M., Umemura, S., Van Der Harst, P., Van Der Schouw, Y.T., Van Gilst, W.H., Vartiainen, E., Vasan, R.S., Veldre, G., Verwoert, G.C., Viigimaa, M., Vinay, D.G., Vineis, P., Voight, B.F., Vollenweider, P., Wagenknecht, L.E., Wain, L.V., Wang, X., Wang, T.J., Wareham, N.J., Watkins, H., Weder, A.B., Whincup, P.H., Wiggins, K.L., Witteman, J.C.M., Wong, A., Wu, Y., Yajnik, C.S., Yao, J., Young, J.H., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, J.H., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, J.-Y., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, S.-C., Wong, T.-Y., Liu, J., Young, T.L., Aung, T., Teo, Y.-Y., Kim, Y.J., Kang, D., Chen, C.-H., Tsai, F.-J., Chang, L.-C., Fann, S.-J.C., Mei, H., Hixson, J.E., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, Y.-T., Tanaka, T., Reilly, M.P., Schunkert, H., Assimes, T.L., Hall, A., Hengstenberg, C., König, I.R., Laaksonen, R., McPherson, R., Thompson, J.R., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, L.A., Halperin, E., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, G.A., Holm, H., Roberts, R., Stewart, A.F.R., 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, K.J., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, H.J., Perret, C., Proust, C., Münzel, T.F., Barbalic, M., Chen, I.Y.-D., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, K.D., Volcik, K., Gretarsdottir, S., Gulcher, J.R., 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, A.K., Willenborg, C., Böhm, B.O., Dobnig, H., Grammer, T.B., Hoffmann, M.M., Meinitzer, A., Winkelmann, B.R., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., 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J.T., Felix, S.B., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, R.J., Greiser, K.H., Deckers, J.W., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, M.M., Werdan, K., Mitchell, G.F., Arnett, D.K., Gottdiener, J.S., Blettner, M., Friedrich, N., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P.S., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L.R., 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.F., 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.L., 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. © 2016, Nature Publishing Group. All rights reserved.

Published
2016

29. CYP2D6 Genotype and Adjuvant Tamoxifen : Meta-Analysis of Heterogeneous Study Populations

Author

Province, M. A., Goetz, M. P., Brauch, H., Flockhare, D. A., Hebert, J. M., Whaley, R., Suman, V. J., Schroth, W., Winter, S., Zembutsu, H., Mushiroda, T., Newman, W. G., Lee, M-TM., Ambrosone, C. B., Beckmann, M. W., Choi, J-Y, Dieudonne, A-S, Fasching, P. A., Ferraldeschi, R., Gong, L., Haschke-Becher, E., Howel, A., Jordan, L. B., Hamann, U., Kiyotani, K., Krippl, P., Lambrechts, D., Latif, A., Langsenlehner, U., Lorizio, W., Neven, P., Nguyen, A. T., Park, B-W., Purdie, C. A., Quinlan, P., Renner, W., Schmidt, M., Schwab, M., Shin, J-G, Stingl, J. C., Wegman, Pia, Wingren, Sten, Wu, A. H. B., Ziv, E., Zirpoli, G., Thompson, A. M., Jordan, V. C., Nakamura, Y., Altman, R. B., Ames, M. M., Klein, T. E., Province, M. A., Goetz, M. P., Brauch, H., Flockhare, D. A., Hebert, J. M., Whaley, R., Suman, V. J., Schroth, W., Winter, S., Zembutsu, H., Mushiroda, T., Newman, W. G., Lee, M-TM., Ambrosone, C. B., Beckmann, M. W., Choi, J-Y, Dieudonne, A-S, Fasching, P. A., Ferraldeschi, R., Gong, L., Haschke-Becher, E., Howel, A., Jordan, L. B., Hamann, U., Kiyotani, K., Krippl, P., Lambrechts, D., Latif, A., Langsenlehner, U., Lorizio, W., Neven, P., Nguyen, A. T., Park, B-W., Purdie, C. A., Quinlan, P., Renner, W., Schmidt, M., Schwab, M., Shin, J-G, Stingl, J. C., Wegman, Pia, Wingren, Sten, Wu, A. H. B., Ziv, E., Zirpoli, G., Thompson, A. M., Jordan, V. C., Nakamura, Y., Altman, R. B., Ames, M. M., and Klein, T. E.

Abstract

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1), CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy., Funding Agencies:National Institutes of Health (National Institute of General Medical Sciences)National Institutes of Health (National Cancer Institute)National Institutes of Health (National Institute of Child Health and Human Development)Breast Cancer Research (Scotland) Tayside Tissue Bank California Breast Cancer Research Program Cancer Research UK Deutsches Krebsforschungszentrum, Heidelberg, Germany Robert Bosch Foundation, Stuttgart, Germany Marie Curie Initial Training Network "FightingDrugFailure" GrantStichting Emmanuel van der Schueren (scientific partner of the Vlaamse Liga tegen Kanker) National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea Deutsche Forschungsgemeinschaft, Germany

Published
2014
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32. Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: The GENOMOS study (vol 3, pg 223, 2006)

Author

Ralston, SH, Uitterlinden, André, Brandi, ML, Balcells, S, Langdahl, BL, Lips, P, Lorenc, R, Obermayer-Pietsch, B, Scollen, S, Bustamante, M, Husted, LB, Carey, AH, Diez-Perez, A, Dunning, AM, Falchetti, A, Karczmarewicz, E, Kruk, M, van Leeuwen, Hans, van Meurs, Joyce, Mangion, J, McGuigan, FEA, Mellibovsky, L, del Monte, F, Pols, Huib, Reeve, J, Reid, DM, Renner, W, Rivadeneira, Fernando, van Schoor, NM, Sherlock, RE, Ioannidis, JPA, and Internal Medicine

Published
2006

35. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Author

International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Ehret, G.B., Munroe, P.B., Rice, K.M., Bochud, M., Johnson, A.D., Chasman, D.I., Smith, A.V., Tobin, M.D., Verwoert, G.C., Hwang, S.J., Pihur, V., Vollenweider, P., O'Reilly, P.F., Amin, N., Bragg-Gresham, J.L., Teumer, A., Glazer, N.L., Launer, L., Zhao, J.H., Aulchenko, Y., Heath, S., Sõber, S., Parsa, A., Luan, J., Arora, P., Dehghan, A., Zhang, F., Lucas, G., Hicks, A.A., Jackson, A.U., Peden, J.F., Tanaka, T., Wild, S.H., Rudan, I., Igl, W., Milaneschi, Y., Parker, A.N., Fava, C., Chambers, J.C., Fox, E.R., Kumari, M., Go, M.J., van der Harst, P., Kao, W.H., Sjögren, M., Vinay, D.G., Alexander, M., Tabara, Y., Shaw-Hawkins, S., Whincup, P.H., Liu, Y., Shi, G., Kuusisto, J., Tayo, B., Seielstad, M., Sim, X., Nguyen, K.D., Lehtimäki, T., Matullo, G., Wu, Y., Gaunt, T.R., Onland-Moret, N.C., Cooper, M.N., Platou, C.G., Org, E., Hardy, R., Dahgam, S., Palmen, J., Vitart, V., Braund, P.S., Kuznetsova, T., Uiterwaal, C.S., Adeyemo, A., Palmas, W., Campbell, H., Ludwig, B., Tomaszewski, M., Tzoulaki, I., Palmer, N.D., Aspelund, T., Garcia, M., Chang, Y.P., O'Connell, J.R., Steinle, N.I., Grobbee, D.E., Arking, D.E., Kardia, S.L., Morrison, A.C., Hernandez, D., Najjar, S., McArdle, W.L., Hadley, D., Brown, M.J., Connell, J.M., Hingorani, A.D., Day, I.N., Lawlor, D.A., Beilby, J.P., Lawrence, R.W., Clarke, R., Hopewell, J.C., Ongen, H., Dreisbach, A.W., Li, Y., Young, J.H., Bis, J.C., Kähönen, M., Viikari, J., Adair, L.S., Lee, N.R., Chen, M.H., Olden, M., Pattaro, C., Bolton, J.A., Köttgen, A., Bergmann, S., Mooser, V., Chaturvedi, N., Frayling, T.M., Islam, M., Jafar, T.H., Erdmann, J., Kulkarni, S.R., Bornstein, S.R., Grässler, J., Groop, L., Voight, B.F., Kettunen, J., Howard, P., Taylor, A., Guarrera, S., Ricceri, F., Emilsson, V., Plump, A., Barroso, I., Khaw, K.T., Weder, A.B., Hunt, S.C., Sun, Y.V., Bergman, R.N., Collins, F.S., Bonnycastle, L.L., Scott, L.J., Stringham, H.M., Peltonen, L., Perola, M., Vartiainen, E., Brand, S.M., Staessen, J.A., Wang, T.J., Burton, P.R., Artigas, M.S., Dong, Y., Snieder, H., Wang, X., Zhu, H., Lohman, K.K., Rudock, M.E., Heckbert, S.R., Smith, N.L., Wiggins, K.L., Doumatey, A., Shriner, D., Veldre, G., Viigimaa, M., Kinra, S., Prabhakaran, D., Tripathy, V., Langefeld, C.D., Rosengren, A., Thelle, D.S., Corsi, A.M., Singleton, A., Forrester, T., Hilton, G., McKenzie, C.A., Salako, T., Iwai, N., Kita, Y., Ogihara, T., Ohkubo, T., Okamura, T., Ueshima, H., Umemura, S., Eyheramendy, S., Meitinger, T., Wichmann, H.E., Cho, Y.S., Kim, H.L., Lee, J.Y., Scott, J., Sehmi, J.S., Zhang, W., Hedblad, B., Nilsson, P., Smith, G.D., Wong, A., Narisu, N., Stančáková, A., Raffel, L.J., Yao, J., Kathiresan, S., O'Donnell, C.J., Schwartz, S.M., Ikram, M.A., Longstreth, W.T., Mosley, T.H., Seshadri, S., Shrine, N.R., Wain, L.V., Morken, M.A., Swift, A.J., Laitinen, J., Prokopenko, I., Zitting, P., Cooper, J.A., Humphries, S.E., Danesh, J., Rasheed, A., Goel, A., Hamsten, A., Watkins, H., Bakker, S.J., van Gilst, W.H., Janipalli, C.S., Mani, K.R., Yajnik, C.S., Hofman, A., Mattace-Raso, F.U., Oostra, B.A., Demirkan, A., Isaacs, A., Rivadeneira, F., Lakatta, E.G., Orru, M., Scuteri, A., Ala-Korpela, M., Kangas, A.J., Lyytikäinen, L.P., Soininen, P., Tukiainen, T., Würtz, P., Ong, R.T., Dörr, M., Kroemer, H.K., Völker, U., Völzke, H., Galan, P., Hercberg, S., Lathrop, M., Zelenika, D., Deloukas, P., Mangino, M., Spector, T.D., Zhai, G., Meschia, J.F., Nalls, M.A., Sharma, P., Terzic, J., Kumar, M.V., Denniff, M., Zukowska-Szczechowska, E., Wagenknecht, L.E., Fowkes, F.G., Charchar, F.J., Schwarz, P.E., Hayward, C., Guo, X., Rotimi, C., Bots, M.L., Brand, E., Samani, N.J., Polasek, O., Talmud, P.J., Nyberg, F., Kuh, D., Laan, M., Hveem, K., Palmer, L.J., van der Schouw, Y.T., Casas, J.P., Mohlke, K.L., Vineis, P., Raitakari, O., Ganesh, S.K., Wong, T.Y., Tai, E.S., Cooper, R.S., Laakso, M., Rao, D.C., Harris, T.B., Morris, R.W., Dominiczak, A.F., Kivimaki, M., Marmot, M.G., Miki, T., Saleheen, D., Chandak, G.R., Coresh, J., Navis, G., Salomaa, V., Han, B.G., Zhu, X., Kooner, J.S., Melander, O., Ridker, P.M., Bandinelli, S., Gyllensten, U.B., Wright, A.F., Wilson, J.F., Ferrucci, L., Farrall, M., Tuomilehto, J., Pramstaller, P.P., Elosua, R., Soranzo, N., Sijbrands, E.J., Altshuler, D., Loos, R.J., Shuldiner, A.R., Gieger, C., Meneton, P., Uitterlinden, A.G., Wareham, N.J., Gudnason, V., Rotter, J.I., Rettig, R., Uda, M., Strachan, D.P., Witteman, J.C., Hartikainen, A.L., Beckmann, J.S., Boerwinkle, E., Vasan, R.S., Boehnke, M., Larson, M.G., Järvelin, M.R., Psaty, B.M., Abecasis, G.R., Chakravarti, A., Elliott, P., van Duijn, C.M., Newton-Cheh, C., Levy, D., Caulfield, M.J., Johnson, T., Tang, H., Knowles, J., Hlatky, M., Fortmann, S., Assimes, T.L., Quertermous, T., Go, A., Iribarren, C., Absher, D., Risch, N., Myers, R., Sidney, S., Ziegler, A., Schillert, A., Bickel, C., Sinning, C., Rupprecht, H.J., Lackner, K., Wild, P., Schnabel, R., Blankenberg, S., Zeller, T., Münzel, T., Perret, C., Cambien, F., Tiret, L., Nicaud, V., Proust, C., Uitterlinden, A., van Duijn, C., Whitteman, J., Cupples, L.A., Demissie-Banjaw, S., Ramachandran, V., Smith, A., Folsom, A., Morrison, A., Chen, I.Y., Bis, J., Volcik, K., Rice, K., Taylor, K.D., Marciante, K., Smith, N., Glazer, N., Heckbert, S., Harris, T., Lumley, T., Kong, A., Thorleifsson, G., Thorgeirsson, G., Holm, H., Gulcher, J.R., Stefansson, K., Andersen, K., Gretarsdottir, S., Thorsteinsdottir, U., Preuss, M., Schreiber, S., König, I.R., Lieb, W., Hengstenberg, C., Schunkert, H., Fischer, 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., Klopp, N., Illig, T., Meinitzer, A., Tomaschitz, A., Halperin, E., Dobnig, H., Scharnagl, H., Kleber, M., Laaksonen, R., Pilz, S., Grammer, T.B., Stojakovic, T., Renner, W., März, W., Böhm, B.O., Winkelmann, B.R., Winkler, K., Hoffmann, M.M., Siscovick, D.S., Musunuru, K., Barbalic, M., Guiducci, C., Burtt, N., Gabriel, S.B., Stewart, A.F., Wells, G.A., Chen, L., Jarinova, O., Roberts, R., McPherson, R., Dandona, S., Pichard, A.D., Rader, D.J., Devaney, J., Lindsay, J.M., Kent, K.M., Qu, L., Satler, L., Burnett, M.S., Li, M., Reilly, M.P., Wilensky, R., Waksman, R., Epstein, S., Matthai, W., Knouff, C.W., Waterworth, D.M., Hakonarson, H.H., Walker, M.C., Hall, A.S., Balmforth, A.J., Wright, B.J., Nelson, C., Thompson, J.R., Ball, S.G., Felix, J.F., Demissie, S., Loehr, L.R., Rosamond, W.D., Folsom, A.R., Benjamin, E., Aulchenko, Y.S., Haritunians, T., Couper, D., Murabito, J., Wang, Y.A., Stricker, B.H., Gottdiener, J.S., Chang, P.P., Willerson, J.T., Böger, C.A., Fuchsberger, C., Gao, X., Yang, Q., Schmidt, H., Ketkar, S., Paré, G., Atkinson, E.J., Lohman, K., Cornelis, M.C., Probst-Hensch, N.M., Kronenberg, F., Tönjes, A., Eiriksdottir, G., Launer, L.J., Rampersaud, E., Mitchell, B.D., Struchalin, M., Cavalieri, M., Giallauria, F., Metter, J., de Boer, J., Siscovick, D., Zillikens, M.C., Feitosa, M., Province, M., de Andrade, M., Turner, S.T., Wild, P.S., Schnabel, R.B., Wilde, S., Munzel, T.F., Leak, T.S., Koenig, W., Zgaga, L., Zemunik, T., Kolcic, I., Minelli, C., Hu, F.B., Johansson, A., Zaboli, G., Ellinghaus, D., Imboden, M., Nitsch, D., Brandstätter, A., Kollerits, B., Kedenko, L., Mägi, R., Stumvoll, M., Kovacs, P., Boban, M., Campbell, S., Endlich, K., Nauck, M., Badola, S., Curhan, G.C., Franke, A., Rochat, T., Paulweber, B., Wang, W., Schmidt, R., Shlipak, M.G., Borecki, I., Krämer, B.K., Gyllensten, U., Hastie, N., Heid, I.M., Fox, C.S., Felix, S.B., Watzinger, N., Homuth, G., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, R.J., Greiser, K.H., Deckers, J.W., Stritzke, J., Lackner, K.J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, M.M., Werdan, K., Mitchell, G.F., Arnett, D.K., Blettner, M., Friedrich, N., Benjamin, E.J., Lord, G.M., Gale, D.P., Wass, M.N., Ahmadi, K.R., Beckmann, J., Bilo, H.J., Cook, H.T., Cotlarciuc, I., Davey Smith, G., de Silva, R., Deng, G., Devuyst, O., Dikkeschei, L.D., Dimkovic, N., Dockrell, M., Dominiczak, A., Ebrahim, S., Eggermann, T., Floege, J., Forouhi, N.G., Gansevoort, R.T., Han, X., Homan van der Heide, J.J., Hepkema, B.G., Hernandez-Fuentes, M., Hypponen, E., de Jong, P.E., Kleefstra, N., Lagou, V., Lapsley, M., Luttropp, K., Maréchal, C., Nordfors, L., Penninx, B.W., Perucha, E., Pouta, A., Roderick, P.J., Ruokonen, A., Sanna, S., Schalling, M., Schlessinger, D., Schlieper, G., Seelen, M.A., Smit, J.H., Stenvinkel, P., Sternberg, M.J., Swaminathan, R., Ubink-Veltmaat, L.J., Wallace, C., Waterworth, D., Zerres, K., Waeber, G., Maxwell, P.H., McCarthy, M.I., Jarvelin, M.R., Lightstone, L., International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Ehret, G.B., Munroe, P.B., Rice, K.M., Bochud, M., Johnson, A.D., Chasman, D.I., Smith, A.V., Tobin, M.D., Verwoert, G.C., Hwang, S.J., Pihur, V., Vollenweider, P., O'Reilly, P.F., Amin, N., Bragg-Gresham, J.L., Teumer, A., Glazer, N.L., Launer, L., Zhao, J.H., Aulchenko, Y., Heath, S., Sõber, S., Parsa, A., Luan, J., Arora, P., Dehghan, A., Zhang, F., Lucas, G., Hicks, A.A., Jackson, A.U., Peden, J.F., Tanaka, T., Wild, S.H., Rudan, I., Igl, W., Milaneschi, Y., Parker, A.N., Fava, C., Chambers, J.C., Fox, E.R., Kumari, M., Go, M.J., van der Harst, P., Kao, W.H., Sjögren, M., Vinay, D.G., Alexander, M., Tabara, Y., Shaw-Hawkins, S., Whincup, P.H., Liu, Y., Shi, G., Kuusisto, J., Tayo, B., Seielstad, M., Sim, X., Nguyen, K.D., Lehtimäki, T., Matullo, G., Wu, Y., Gaunt, T.R., Onland-Moret, N.C., Cooper, M.N., Platou, C.G., Org, E., Hardy, R., Dahgam, S., Palmen, J., Vitart, V., Braund, P.S., Kuznetsova, T., Uiterwaal, C.S., Adeyemo, A., Palmas, W., Campbell, H., Ludwig, B., Tomaszewski, M., Tzoulaki, I., Palmer, N.D., Aspelund, T., Garcia, M., Chang, Y.P., O'Connell, J.R., Steinle, N.I., Grobbee, D.E., Arking, D.E., Kardia, S.L., Morrison, A.C., Hernandez, D., Najjar, S., McArdle, W.L., Hadley, D., Brown, M.J., Connell, J.M., Hingorani, A.D., Day, I.N., Lawlor, D.A., Beilby, J.P., Lawrence, R.W., Clarke, R., Hopewell, J.C., Ongen, H., Dreisbach, A.W., Li, Y., Young, J.H., Bis, J.C., Kähönen, M., Viikari, J., Adair, L.S., Lee, N.R., Chen, M.H., Olden, M., Pattaro, C., Bolton, J.A., Köttgen, A., Bergmann, S., Mooser, V., Chaturvedi, N., Frayling, T.M., Islam, M., Jafar, T.H., Erdmann, J., Kulkarni, S.R., Bornstein, S.R., Grässler, J., Groop, L., Voight, B.F., Kettunen, J., Howard, P., Taylor, A., Guarrera, S., Ricceri, F., Emilsson, V., Plump, A., Barroso, I., Khaw, K.T., Weder, A.B., Hunt, S.C., Sun, Y.V., Bergman, R.N., Collins, F.S., Bonnycastle, L.L., Scott, L.J., Stringham, H.M., Peltonen, L., Perola, M., Vartiainen, E., Brand, S.M., Staessen, J.A., Wang, T.J., Burton, P.R., Artigas, M.S., Dong, Y., Snieder, H., Wang, X., Zhu, H., Lohman, K.K., Rudock, M.E., Heckbert, S.R., Smith, N.L., Wiggins, K.L., Doumatey, A., Shriner, D., Veldre, G., Viigimaa, M., Kinra, S., Prabhakaran, D., Tripathy, V., Langefeld, C.D., Rosengren, A., Thelle, D.S., Corsi, A.M., Singleton, A., Forrester, T., Hilton, G., McKenzie, C.A., Salako, T., Iwai, N., Kita, Y., Ogihara, T., Ohkubo, T., Okamura, T., Ueshima, H., Umemura, S., Eyheramendy, S., Meitinger, T., Wichmann, H.E., Cho, Y.S., Kim, H.L., Lee, J.Y., Scott, J., Sehmi, J.S., Zhang, W., Hedblad, B., Nilsson, P., Smith, G.D., Wong, A., Narisu, N., Stančáková, A., Raffel, L.J., Yao, J., Kathiresan, S., O'Donnell, C.J., Schwartz, S.M., Ikram, M.A., Longstreth, W.T., Mosley, T.H., Seshadri, S., Shrine, N.R., Wain, L.V., Morken, M.A., Swift, A.J., Laitinen, J., Prokopenko, I., Zitting, P., Cooper, J.A., Humphries, S.E., Danesh, J., Rasheed, A., Goel, A., Hamsten, A., Watkins, H., Bakker, S.J., van Gilst, W.H., Janipalli, C.S., Mani, K.R., Yajnik, C.S., Hofman, A., Mattace-Raso, F.U., Oostra, B.A., Demirkan, A., Isaacs, A., Rivadeneira, F., Lakatta, E.G., Orru, M., Scuteri, A., Ala-Korpela, M., Kangas, A.J., Lyytikäinen, L.P., Soininen, P., Tukiainen, T., Würtz, P., Ong, R.T., Dörr, M., Kroemer, H.K., Völker, U., Völzke, H., Galan, P., Hercberg, S., Lathrop, M., Zelenika, D., Deloukas, P., Mangino, M., Spector, T.D., Zhai, G., Meschia, J.F., Nalls, M.A., Sharma, P., Terzic, J., Kumar, M.V., Denniff, M., Zukowska-Szczechowska, E., Wagenknecht, L.E., Fowkes, F.G., Charchar, F.J., Schwarz, P.E., Hayward, C., Guo, X., Rotimi, C., Bots, M.L., Brand, E., Samani, N.J., Polasek, O., Talmud, P.J., Nyberg, F., Kuh, D., Laan, M., Hveem, K., Palmer, L.J., van der Schouw, Y.T., Casas, J.P., Mohlke, K.L., Vineis, P., Raitakari, O., Ganesh, S.K., Wong, T.Y., Tai, E.S., Cooper, R.S., Laakso, M., Rao, D.C., Harris, T.B., Morris, R.W., Dominiczak, A.F., Kivimaki, M., Marmot, M.G., Miki, T., Saleheen, D., Chandak, G.R., Coresh, J., Navis, G., Salomaa, V., Han, B.G., Zhu, X., Kooner, J.S., Melander, O., Ridker, P.M., Bandinelli, S., Gyllensten, U.B., Wright, A.F., Wilson, J.F., Ferrucci, L., Farrall, M., Tuomilehto, J., Pramstaller, P.P., Elosua, R., Soranzo, N., Sijbrands, E.J., Altshuler, D., Loos, R.J., Shuldiner, A.R., Gieger, C., Meneton, P., Uitterlinden, A.G., Wareham, N.J., Gudnason, V., Rotter, J.I., Rettig, R., Uda, M., Strachan, D.P., Witteman, J.C., Hartikainen, A.L., Beckmann, J.S., Boerwinkle, E., Vasan, R.S., Boehnke, M., Larson, M.G., Järvelin, M.R., Psaty, B.M., Abecasis, G.R., Chakravarti, A., Elliott, P., van Duijn, C.M., Newton-Cheh, C., Levy, D., Caulfield, M.J., Johnson, T., Tang, H., Knowles, J., Hlatky, M., Fortmann, S., Assimes, T.L., Quertermous, T., Go, A., Iribarren, C., Absher, D., Risch, N., Myers, R., Sidney, S., Ziegler, A., Schillert, A., Bickel, C., Sinning, C., Rupprecht, H.J., Lackner, K., Wild, P., Schnabel, R., Blankenberg, S., Zeller, T., Münzel, T., Perret, C., Cambien, F., Tiret, L., Nicaud, V., Proust, C., Uitterlinden, A., van Duijn, C., Whitteman, J., Cupples, L.A., Demissie-Banjaw, S., Ramachandran, V., Smith, A., Folsom, A., Morrison, A., Chen, I.Y., Bis, J., Volcik, K., Rice, K., Taylor, K.D., Marciante, K., Smith, N., Glazer, N., Heckbert, S., Harris, T., Lumley, T., Kong, A., Thorleifsson, G., Thorgeirsson, G., Holm, H., Gulcher, J.R., Stefansson, K., Andersen, K., Gretarsdottir, S., Thorsteinsdottir, U., Preuss, M., Schreiber, S., König, I.R., Lieb, W., Hengstenberg, C., Schunkert, H., Fischer, 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., Klopp, N., Illig, T., Meinitzer, A., Tomaschitz, A., Halperin, E., Dobnig, H., Scharnagl, H., Kleber, M., Laaksonen, R., Pilz, S., Grammer, T.B., Stojakovic, T., Renner, W., März, W., Böhm, B.O., Winkelmann, B.R., Winkler, K., Hoffmann, M.M., Siscovick, D.S., Musunuru, K., Barbalic, M., Guiducci, C., Burtt, N., Gabriel, S.B., Stewart, A.F., Wells, G.A., Chen, L., Jarinova, O., Roberts, R., McPherson, R., Dandona, S., Pichard, A.D., Rader, D.J., Devaney, J., Lindsay, J.M., Kent, K.M., Qu, L., Satler, L., Burnett, M.S., Li, M., Reilly, M.P., Wilensky, R., Waksman, R., Epstein, S., Matthai, W., Knouff, C.W., Waterworth, D.M., Hakonarson, H.H., Walker, M.C., Hall, A.S., Balmforth, A.J., Wright, B.J., Nelson, C., Thompson, J.R., Ball, S.G., Felix, J.F., Demissie, S., Loehr, L.R., Rosamond, W.D., Folsom, A.R., Benjamin, E., Aulchenko, Y.S., Haritunians, T., Couper, D., Murabito, J., Wang, Y.A., Stricker, B.H., Gottdiener, J.S., Chang, P.P., Willerson, J.T., Böger, C.A., Fuchsberger, C., Gao, X., Yang, Q., Schmidt, H., Ketkar, S., Paré, G., Atkinson, E.J., Lohman, K., Cornelis, M.C., Probst-Hensch, N.M., Kronenberg, F., Tönjes, A., Eiriksdottir, G., Launer, L.J., Rampersaud, E., Mitchell, B.D., Struchalin, M., Cavalieri, M., Giallauria, F., Metter, J., de Boer, J., Siscovick, D., Zillikens, M.C., Feitosa, M., Province, M., de Andrade, M., Turner, S.T., Wild, P.S., Schnabel, R.B., Wilde, S., Munzel, T.F., Leak, T.S., Koenig, W., Zgaga, L., Zemunik, T., Kolcic, I., Minelli, C., Hu, F.B., Johansson, A., Zaboli, G., Ellinghaus, D., Imboden, M., Nitsch, D., Brandstätter, A., Kollerits, B., Kedenko, L., Mägi, R., Stumvoll, M., Kovacs, P., Boban, M., Campbell, S., Endlich, K., Nauck, M., Badola, S., Curhan, G.C., Franke, A., Rochat, T., Paulweber, B., Wang, W., Schmidt, R., Shlipak, M.G., Borecki, I., Krämer, B.K., Gyllensten, U., Hastie, N., Heid, I.M., Fox, C.S., Felix, S.B., Watzinger, N., Homuth, G., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, R.J., Greiser, K.H., Deckers, J.W., Stritzke, J., Lackner, K.J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, M.M., Werdan, K., Mitchell, G.F., Arnett, D.K., Blettner, M., Friedrich, N., Benjamin, E.J., Lord, G.M., Gale, D.P., Wass, M.N., Ahmadi, K.R., Beckmann, J., Bilo, H.J., Cook, H.T., Cotlarciuc, I., Davey Smith, G., de Silva, R., Deng, G., Devuyst, O., Dikkeschei, L.D., Dimkovic, N., Dockrell, M., Dominiczak, A., Ebrahim, S., Eggermann, T., Floege, J., Forouhi, N.G., Gansevoort, R.T., Han, X., Homan van der Heide, J.J., Hepkema, B.G., Hernandez-Fuentes, M., Hypponen, E., de Jong, P.E., Kleefstra, N., Lagou, V., Lapsley, M., Luttropp, K., Maréchal, C., Nordfors, L., Penninx, B.W., Perucha, E., Pouta, A., Roderick, P.J., Ruokonen, A., Sanna, S., Schalling, M., Schlessinger, D., Schlieper, G., Seelen, M.A., Smit, J.H., Stenvinkel, P., Sternberg, M.J., Swaminathan, R., Ubink-Veltmaat, L.J., Wallace, C., Waterworth, D., Zerres, K., Waeber, G., Maxwell, P.H., McCarthy, M.I., Jarvelin, M.R., and Lightstone, L.

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.

Published
2011

36. RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Author

Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Moll, F.L. (Frans), Boerwinkle, E.A. (Eric), Hall, A. (Anne), Hengstenberg, C. (Christian), König, I.R. (Inke), Laaksonen, R. (Reijo), McPherson, R. (Ruth), Thompson, J.R. (John), Thorsteinsdottir, U. (Unnur), Ziegler, A. (Andreas), Koenig, W. (Wolfgang), Chen, L. (Li), Cupples, L.A. (Adrienne), Halperin, E. (Eran), Musunuru, K. (Kiran), Preuss, M. (Michael), Schillert, A. (Arne), Thorleifsson, G. (Gudmar), Voight, B.F. (Benjamin), Wells, G.A. (George), Deloukas, P. (Panagiotis), Holm, H. (Hilma), Roberts, R. (Robert), Stewart, A.F.R. (Alexandre), Fortmann, S.P. (Stephen), Go, A.T.J.I. (Attie), Hlatky, M.A. (Mark), Iribarren, C. (Carlos), Knowles, J.W. (Joshua), Myers, R.H. (Richard), Quertermous, T. (Thomas), Sidney, S. (Steven), Risch, N., Tang, H. (Hui), Blankenberg, S. (Stefan), Zeller, T. (Tanja), Wild, P.S. (Philipp), Schnabel, R.B. (Renate), Sinning, C. (Christoph), Lackner, K.J. (Karl), Tiret, L. (Laurence), Nicaud, V., Cambien, F. (François), Bickel, H. (Horst), Rupprecht, H.J., Perret, C. (Claire), Proust, C. (Carole), Munzel, T. (Thomas), Barbalic, M. (maja), Bis, J.C. (Joshua), Chen, I.Y.-D. (Ida Yii-Der), Dehghan, A. (Abbas), Demissie-Banjaw, S. (Serkalem), Folsom, A.R. (Aaron), Glazer, N.L. (Nicole), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Levy, D. (Daniel), Lumley, T. (Thomas), Marciante, K. (Kristin), Morrison, A.C. (Alanna), O'Donnell, C.J. (Christopher), Psaty, B.M. (Bruce), Rice, K. (Kenneth), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Smith, N.L. (Nicholas), Smith, A.V. (Davey), Taylor, K.D. (Kent), Duijn, C.M. (Cornelia) van, Volcik, K.A. (Kelly), Whitteman, J. (Jaqueline), Ramachandran, V.S. (Vasan), Hofman, A. (Albert), Uitterlinden, A.G. (André), Gretarsdottir, S. (Solveig), Gulcher, J.R. (Jeffrey), Kong, A. (Augustine), Zwart, J-A. (John-Anker), Thorgeirsson, G. (Gudmundur), Andersen, K.K. (Karl), Fischer, M. (Marcus), Großhennig, A. (Anika), Lieb, W. (Wolfgang), Linsel-Nitschke, P. (Patrick), Stark, K. (Klaus), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Aherrahrou, Z. (Zouhair), Bruse, P. (Petra), Doering, A. (Angela), Illig, T. (Thomas), Klopp, N. (Norman), Loley, C. (Christina), Medack, A. (Anja), Meisinger, C. (Christa), Meitinger, T. (Thomas), Nahrstedt, J. (Janja), Peters, A. (Annette), Wagner, A.K. (Arnika), Willenborg, C. (Christina), Böhm, B., Dobnig, H. (Harald), Grammer, T.B. (Tanja), Hoffmann, M.M. (Michael), Kleber, M. (Martina), März, W. (Winfried), Meinitzer, A. (Andreas), Winkelmann, B., Pilz, D.T. (Daniela), Renner, W. (Wilfried), Scharnagl, H. (Hubert), Stojakovic, T. (Tatjana), Tomaschitz, A. (Andreas), Winkler, K. (Karl), Guiducci, C. (Candace), Burtt, N.P. (Noël), Gabriel, S.B. (Stacey), Elosua, R. (Roberto), Peltonen, L. (Leena Johanna), Salomaa, V. (Veikko), Schwartz, S.M. (Stephen), Melander, O. (Olle), Altshuler, D. (David), Dandona, S. (Sonny), Jarinova, O. (Olga), Qu, L. (Liming), Wilensky, A. (Asaf), Matthai, W. (William), Hakonarson, H. (Hakon), Devaney, J. (Joseph), Burnett, M.S., Pichard, A.D., Kent, K.M. (Kenneth), Satler, L.F., Lindsay, J.M. (Joseph), Waksman, R. (Ron), Knouff, C.W. (Christopher), Waterworth, D. (Dawn), Walker, M.C. (Max), Mooser, V. (Vincent), Epstein, S.E. (Stephen), Rader, D.J. (Daniel), Braund, P.S. (Peter), Nelson, C.P. (Christopher P.), Li, M. (Mingyao), Wright, B.J. (Benjamin), Balmforth, A.J. (Anthony), Ball, S.G. (Stephen), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Moll, F.L. (Frans), Boerwinkle, E.A. (Eric), Hall, A. (Anne), Hengstenberg, C. (Christian), König, I.R. (Inke), Laaksonen, R. (Reijo), McPherson, R. (Ruth), Thompson, J.R. (John), Thorsteinsdottir, U. (Unnur), Ziegler, A. (Andreas), Koenig, W. (Wolfgang), Chen, L. (Li), Cupples, L.A. (Adrienne), Halperin, E. (Eran), Musunuru, K. (Kiran), Preuss, M. (Michael), Schillert, A. (Arne), Thorleifsson, G. (Gudmar), Voight, B.F. (Benjamin), Wells, G.A. (George), Deloukas, P. (Panagiotis), Holm, H. (Hilma), Roberts, R. (Robert), Stewart, A.F.R. (Alexandre), Fortmann, S.P. (Stephen), Go, A.T.J.I. (Attie), Hlatky, M.A. (Mark), Iribarren, C. (Carlos), Knowles, J.W. (Joshua), Myers, R.H. (Richard), Quertermous, T. (Thomas), Sidney, S. (Steven), Risch, N., Tang, H. (Hui), Blankenberg, S. (Stefan), Zeller, T. (Tanja), Wild, P.S. (Philipp), Schnabel, R.B. (Renate), Sinning, C. (Christoph), Lackner, K.J. (Karl), Tiret, L. (Laurence), Nicaud, V., Cambien, F. (François), Bickel, H. (Horst), Rupprecht, H.J., Perret, C. (Claire), Proust, C. (Carole), Munzel, T. (Thomas), Barbalic, M. (maja), Bis, J.C. (Joshua), Chen, I.Y.-D. (Ida Yii-Der), Dehghan, A. (Abbas), Demissie-Banjaw, S. (Serkalem), Folsom, A.R. (Aaron), Glazer, N.L. (Nicole), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Levy, D. (Daniel), Lumley, T. (Thomas), Marciante, K. (Kristin), Morrison, A.C. (Alanna), O'Donnell, C.J. (Christopher), Psaty, B.M. (Bruce), Rice, K. (Kenneth), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Smith, N.L. (Nicholas), Smith, A.V. (Davey), Taylor, K.D. (Kent), Duijn, C.M. (Cornelia) van, Volcik, K.A. (Kelly), Whitteman, J. (Jaqueline), Ramachandran, V.S. (Vasan), Hofman, A. (Albert), Uitterlinden, A.G. (André), Gretarsdottir, S. (Solveig), Gulcher, J.R. (Jeffrey), Kong, A. (Augustine), Zwart, J-A. (John-Anker), Thorgeirsson, G. (Gudmundur), Andersen, K.K. (Karl), Fischer, M. (Marcus), Großhennig, A. (Anika), Lieb, W. (Wolfgang), Linsel-Nitschke, P. (Patrick), Stark, K. (Klaus), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Aherrahrou, Z. (Zouhair), Bruse, P. (Petra), Doering, A. (Angela), Illig, T. (Thomas), Klopp, N. (Norman), Loley, C. (Christina), Medack, A. (Anja), Meisinger, C. (Christa), Meitinger, T. (Thomas), Nahrstedt, J. (Janja), Peters, A. (Annette), Wagner, A.K. (Arnika), Willenborg, C. (Christina), Böhm, B., Dobnig, H. (Harald), Grammer, T.B. (Tanja), Hoffmann, M.M. (Michael), Kleber, M. (Martina), März, W. (Winfried), Meinitzer, A. (Andreas), Winkelmann, B., Pilz, D.T. (Daniela), Renner, W. (Wilfried), Scharnagl, H. (Hubert), Stojakovic, T. (Tatjana), Tomaschitz, A. (Andreas), Winkler, K. (Karl), Guiducci, C. (Candace), Burtt, N.P. (Noël), Gabriel, S.B. (Stacey), Elosua, R. (Roberto), Peltonen, L. (Leena Johanna), Salomaa, V. (Veikko), Schwartz, S.M. (Stephen), Melander, O. (Olle), Altshuler, D. (David), Dandona, S. (Sonny), Jarinova, O. (Olga), Qu, L. (Liming), Wilensky, A. (Asaf), Matthai, W. (William), Hakonarson, H. (Hakon), Devaney, J. (Joseph), Burnett, M.S., Pichard, A.D., Kent, K.M. (Kenneth), Satler, L.F., Lindsay, J.M. (Joseph), Waksman, R. (Ron), Knouff, C.W. (Christopher), Waterworth, D. (Dawn), Walker, M.C. (Max), Mooser, V. (Vincent), Epstein, S.E. (Stephen), Rader, D.J. (Daniel), Braund, P.S. (Peter), Nelson, C.P. (Christopher P.), Li, M. (Mingyao), Wright, B.J. (Benjamin), Balmforth, A.J. (Anthony), and Ball, S.G. (Stephen)

Abstract

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4

Published
2011
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37. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis

Author

Meurs, J.B.J. (Joyce) van, Trikalinos, T.A. (Thomas), Ralston, S.H. (Stuart), Balcells, S. (Susana), Brandi, M.L., Brixen, K. (Kim), Kiel, D.P. (Douglas), Langdahl, B.L. (Bente), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Obermayer-Pietsch, B. (Barbara), Ohlsson, C. (Claes), Pettersson, U. (Ulrika), Reid, D.M. (David), Rousseau, M.F. (Francois), Scollen, S. (Serena), Van Hul, W. (Wim), Agueda, L. (Lidia), Åkesson, K. (Kristina), Benevolenskaya, L.I. (Lidia), Ferrari, S.L. (Serge), Hallmans, G. (Göran), Hofman, A. (Albert), Husted, L.B. (Lise Bjerre), Kruk, M. (Marcin), Kaptoge, S. (Stephen), Karasik, D. (David), Karlsson, M. (Magnus), Lorentzon, M. (Mattias), Masi, L. (Laura), McGuigan, F.E., Mellström, D. (Dan), Mosekilde, L. (Leif), Nogues, X. (Xavier), Pols, H.A.P. (Huib), Reeve, J. (Jonathan), Renner, W. (Wilfried), Rivadeneira Ramirez, F. (Fernando), Schoor, N.M. (Natasja) van, Weber, K. (Kurt), Ioannidis, J.P.A. (John), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Trikalinos, T.A. (Thomas), Ralston, S.H. (Stuart), Balcells, S. (Susana), Brandi, M.L., Brixen, K. (Kim), Kiel, D.P. (Douglas), Langdahl, B.L. (Bente), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Obermayer-Pietsch, B. (Barbara), Ohlsson, C. (Claes), Pettersson, U. (Ulrika), Reid, D.M. (David), Rousseau, M.F. (Francois), Scollen, S. (Serena), Van Hul, W. (Wim), Agueda, L. (Lidia), Åkesson, K. (Kristina), Benevolenskaya, L.I. (Lidia), Ferrari, S.L. (Serge), Hallmans, G. (Göran), Hofman, A. (Albert), Husted, L.B. (Lise Bjerre), Kruk, M. (Marcin), Kaptoge, S. (Stephen), Karasik, D. (David), Karlsson, M. (Magnus), Lorentzon, M. (Mattias), Masi, L. (Laura), McGuigan, F.E., Mellström, D. (Dan), Mosekilde, L. (Leif), Nogues, X. (Xavier), Pols, H.A.P. (Huib), Reeve, J. (Jonathan), Renner, W. (Wilfried), Rivadeneira Ramirez, F. (Fernando), Schoor, N.M. (Natasja) van, Weber, K. (Kurt), Ioannidis, J.P.A. (John), and Uitterlinden, A.G. (André)

Abstract

Context: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. Objective: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. Design and Setting: Prospective, multicenter, collaborative study of individuallevel data on 37 534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. Main Outcome Measures: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. Results: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n=25 052 [number of participants with available data]; 20-mg/cm2lower BMD per Met667 allele copy; P=3.3 × 10-8), as was the Val1330 allele (n=24 812; 14-mg/cm2lower BMD per Val1330 copy; P=2.6 × 10-9). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2(P=3.8 × 10-5) and 8 mg/cm2(P=5.0 × 10-6) for the Met667 and Val1330 alleles, respectively (n=25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20 096 individuals]). Risk of all fract

Published
2008
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39. Large-scale evidence for the effect of the COLIA1 Sp1 Polymorphism on Osteoporosis Outcomes: The GENOMOS study

Author

Ralston, S.H. (Stuart), Uitterlinden, A.G. (André), Brandi, M.L., Balcells, S. (Susana), Langdahl, B.L. (Bente), Lips, P. (Paul), Lorenc, R. (Roman), Obermayer-Pietsch, B. (Barbara), Scollen, S. (Serena), Bustamante, M. (Mariona), Husted, L.B. (Lise Bjerre), Carey, A. (Alisoun), Diez-Perez, A. (Adolfo), Dunning, A.M. (Alison), Falchetti, A., Karczmarewicz, E. (Elzbieta), Kruk, M. (Marcin), Leeuwen, J.P.T.M. (Hans) van, Meurs, J.B.J. (Joyce) van, Mangion, J. (Jon), McGuigan, F.E., Mellibovsky, L. (Leonardo), Del Monte, F. (Francesca), Pols, H.A.P. (Huib), Reeve, J. (Jonathan), Reid, D.M. (David), Renner, W. (Wilfried), Rivadeneira Ramirez, F. (Fernando), Schoor, N.M. (Natasja) van, Sherlock, J.K. (Jon), Ioannidis, J.P.A. (John), Ralston, S.H. (Stuart), Uitterlinden, A.G. (André), Brandi, M.L., Balcells, S. (Susana), Langdahl, B.L. (Bente), Lips, P. (Paul), Lorenc, R. (Roman), Obermayer-Pietsch, B. (Barbara), Scollen, S. (Serena), Bustamante, M. (Mariona), Husted, L.B. (Lise Bjerre), Carey, A. (Alisoun), Diez-Perez, A. (Adolfo), Dunning, A.M. (Alison), Falchetti, A., Karczmarewicz, E. (Elzbieta), Kruk, M. (Marcin), Leeuwen, J.P.T.M. (Hans) van, Meurs, J.B.J. (Joyce) van, Mangion, J. (Jon), McGuigan, F.E., Mellibovsky, L. (Leonardo), Del Monte, F. (Francesca), Pols, H.A.P. (Huib), Reeve, J. (Jonathan), Reid, D.M. (David), Renner, W. (Wilfried), Rivadeneira Ramirez, F. (Fernando), Schoor, N.M. (Natasja) van, Sherlock, J.K. (Jon), and Ioannidis, J.P.A. (John)

Abstract

Background: Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COL

Published
2006
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48. The supposed demise of Fordism: Implications for distance education and higher education

Author

Campion, M., Renner, W., Campion, M., and Renner, W.

Abstract

The recent shift in Australian Government policy for Distance Education at the Higher Education level, as intimated by the increasing usage of the notion, Open Learning, is outlined. Such an emphasis on Open Learning contrasts markedly with the concerted effort to centralise and rationalise distance education in the late 1980s. This shift is related to a more general debate concerning the restructuring of industry which is formulated using an analysis grounded in the conceptualisation of Fordism, its crisis and its likely successor. The complex and contested nature of the debate about Fordism is revealed, as is its important connection with postmodernism. The relevance of this broader debate to higher education is then displayed and linked to the particular place of academic staff and their opportunity and ability to influence future policy.

Published
1992

49. VEGF 936C <GT>T polymorphism and association of BI-RADS score in women with suspected breast cancer.

Author

Wehrschuetz M, Schöllnast H, Wehrschuetz E, Renner W, and Luschin G

Abstract

Purpose: Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumors. A 936C > T polymorphism in the VEGF gene has been associated with reduced VEGF plasma levels. Purpose of the present study was to analyze the potential association between VEGF genotype and radiological appearance of breast lesions by mammography. Materials and Methods: Fifty two women with 54 suspected breast lesions were analyzed by the use of mammography with the standard breast imaging reporting and data systems (BI-RADS). Germline VEGF genotype was determined in all subjects by allele-specific digestion of amplification products. An open biopsy was performed on all lesions. Results: VEGF CC, CT and TT genotypes were found in 41 (79%), 9 (17%) and 2 (4%) patients. By mammography 26, 16 and 12 suspected breast lesions were classified as BI-RADS scores 3, 4 and 5, respectively. Both carriers of the TT genotype were classified as BI-RADS 5, whereas among CT or CC carriers, BI-RADS scores 3, 4 and 5 were found in 26, 16 and 10 subjects (P < 0.026). Conclusion: The VEGF 936C > T polymorphism seems to be associated with a high BI-RADS score in women with suspicious breast lesions. [ABSTRACT FROM AUTHOR]

Published
2009

50. TNF-α promoter polymorphisms and primary open-angle glaucoma.

Author

Mossböck, G., Weger, M., Moray, M., Renner, W., Haller-Schober, E. M., Mattes, D., Schmut, O., Wegscheider, B., and El-Shabrawi, Y.

Subjects
MEDICAL genetics, OPEN-angle glaucoma, TUMOR necrosis factors, GENETIC polymorphisms, POLYMERASE chain reaction
Abstract

PurposePrimary open-angle glaucoma (POAG) is a multifactorial optic neuropathy with a strong hereditary component. Recent studies suggested a role for tumour necrosis factor-α(TNF-α) in the pathogenesis of POAG. The purpose of the present study was to investigate a hypothesized association between the TNF-α−308G>A and −238G>A gene polymorphisms and the presence of POAG in a Caucasian population.MethodsThe present case–control study comprised 114 unrelated patients with POAG and 228 healthy control subjects, matched for age and gender. Genotyping of the TNF-α−308G>A and −238G>A polymorphisms was performed using polymerase chain reaction.ResultsAllelic frequencies and genotype distributions of both the TNF-α−308G>A and −238G>A gene polymorphisms did not significantly differ between patients with POAG and control subjects. Presence of the TNF-α−308A-allele was associated with an odds ratio (OR) of 0.96 for POAG, whereas an OR of 0.52 was found among carriers of the TNF-α−238A-allele.ConclusionOur data suggest that none of the investigated TNF-αgene polymorphisms is a major risk factor among Caucasian patients with POAG.Eye (2006) 20, 1040–1043. doi:10.1038/sj.eye.6702078; published online 2 September 2005 [ABSTRACT FROM AUTHOR]

Published
2006
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