11 results on '"Pramstaller, Peter Paul"'
Search Results
2. Ten years of dynamic consent in the CHRIS study: informed consent as a dynamic process
- Author
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Mascalzoni, Deborah, Melotti, Roberto, Pattaro, Cristian, Pramstaller, Peter Paul, Gögele, Martin, De Grandi, Alessandro, and Biasiotto, Roberta
- Published
- 2022
- Full Text
- View/download PDF
3. NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality
- Author
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Böger, Carsten A., Gorski, Mathias, McMahon, Gearoid M., Xu, Huichun, Chang, Yen-Pei C., van der Most, Peter J., Navis, Gerjan, Nolte, Ilja M., de Borst, Martin H., Zhang, Weihua, Lehne, Benjamin, Loh, Marie, Tan, Sian-Tsung, Boerwinkle, Eric, Grams, Morgan E., Sekula, Peggy, Li, Man, Wilmot, Beth, Moon, James G., Scheet, Paul, Cucca, Francesco, Xiao, Xiangjun, Lyytikäinen, Leo-Pekka, Delgado, Graciela, Grammer, Tanja B., Kleber, Marcus E., Sedaghat, Sanaz, Rivadeneira, Fernando, Corre, Tanguy, Kutalik, Zoltan, Bergmann, Sven, Nielson, Carrie M., Srikanth, Priya, Teumer, Alexander, Müller-Nurasyid, Martina, Brockhaus, Anne Catharina, Pfeufer, Arne, Rathmann, Wolfgang, Peters, Annette, Matsumoto, Martha, de Andrade, Mariza, Atkinson, Elizabeth J., Robinson-Cohen, Cassianne, de Boer, Ian H., Hwang, Shih-Jen, Heid, Iris M., Gögele, Martin, Concas, Maria Pina, Tanaka, Toshiko, Bandinelli, Stefania, Nalls, Mike A., Singleton, Andrew, Tajuddin, Salman M., Adeyemo, Adebowale, Zhou, Jie, Doumatey, Ayo, McWeeney, Shannon, Murabito, Joanne, Franceschini, Nora, Flessner, Michael, Shlipak, Michael, Wilson, James G., Chen, Guanjie, Rotimi, Charles N., Zonderman, Alan B., Evans, Michele K., Ferrucci, Luigi, Devuyst, Olivier, Pirastu, Mario, Shuldiner, Alan, Hicks, Andrew A., Pramstaller, Peter Paul, Kestenbaum, Bryan, Kardia, Sharon L.R., Turner, Stephen T., Study, LifeLines Cohort, Briske, Tamara Ellefson, Gieger, Christian, Strauch, Konstantin, Meisinger, Christa, Meitinger, Thomas, Völker, Uwe, Nauck, Matthias, Völzke, Henry, Vollenweider, Peter, Bochud, Murielle, Waeber, Gerard, Kähönen, Mika, Lehtimäki, Terho, März, Winfried, Dehghan, Abbas, Franco, Oscar H., Uitterlinden, Andre G., Hofman, Albert, Taylor, Herman A., Chambers, John C., Kooner, Jaspal S., Fox, Caroline S., Hitzemann, Robert, Orwoll, Eric S., Pattaro, Cristian, Schlessinger, David, Köttgen, Anna, Snieder, Harold, Parsa, Afshin, Cohen, David M., Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, N., G., Rots, Marianne G., S., H., Swertz, Morris, Wolffenbuttel, Bruce H.R., and Wijmenga, Cisca
- Published
- 2017
- Full Text
- View/download PDF
4. Metabolic Signature of Arrhythmogenic Cardiomyopathy
- Author
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Volani, Chiara, primary, Rainer, Johannes, additional, Hernandes, Vinicius Veri, additional, Meraviglia, Viviana, additional, Pramstaller, Peter Paul, additional, Smárason, Sigurður Vidir, additional, Pompilio, Giulio, additional, Casella, Michela, additional, Sommariva, Elena, additional, Paglia, Giuseppe, additional, and Rossini, Alessandra, additional
- Published
- 2021
- Full Text
- View/download PDF
5. NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality
- Author
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UCL - SSS/IREC/NEFR - Pôle de Néphrologie, Böger, Carsten A., Gorski, Mathias, McMahon, Gearoid M., Xu, Huichun, Chang, Yen-Pei C., van der Most, Peter J., Navis, Gerjan, Nolte, Ilja M., de Borst, Martin H., Zhang, Weihua, Lehne, Benjamin, Loh, Marie, Tan, Sian-Tsung, Boerwinkle, Eric, Grams, Morgan E., Sekula, Peggy, Li, Man, Wilmot, Beth, Moon, James G., Scheet, Paul, Cucca, Francesco, Xiao, Xiangjun, Lyytikäinen, Leo-Pekka, Delgado, Graciela, Grammer, Tanja B., Kleber, Marcus E., Sedaghat, Sanaz, Rivadeneira, Fernando, Corre, Tanguy, Kutalik, Zoltan, Bergmann, Sven, Nielson, Carrie M., Srikanth, Priya, Teumer, Alexander, Müller-Nurasyid, Martina, Brockhaus, Anne Catharina, Pfeufer, Arne, Rathmann, Wolfgang, Peters, Annette, Matsumoto, Martha, de Andrade, Mariza, Atkinson, Elizabeth J., Robinson-Cohen, Cassianne, de Boer, Ian H., Hwang, Shih-Jen, Heid, Iris M., Gögele, Martin, Concas, Maria Pina, Tanaka, Toshiko, Bandinelli, Stefania, Nalls, Mike A., Singleton, Andrew, Tajuddin, Salman M., Adeyemo, Adebowale, Zhou, Jie, Doumatey, Ayo, McWeeney, Shannon, Murabito, Joanne, Franceschini, Nora, Flessner, Michael, Shlipak, Michael, Wilson, James G., Chen, Guanjie, Rotimi, Charles N., Zonderman, Alan B., Evans, Michele K., Ferrucci, Luigi, Devuyst, Olivier, Pirastu, Mario, Shuldiner, Alan, Hicks, Andrew A., Pramstaller, Peter Paul, Kestenbaum, Bryan, Kardia, Sharon L.R., Turner, Stephen T., Study, LifeLines Cohort, Briske, Tamara Ellefson, Gieger, Christian, Strauch, Konstantin, Meisinger, Christa, Meitinger, Thomas, Völker, Uwe, Nauck, Matthias, Völzke, Henry, Vollenweider, Peter, Bochud, Murielle, Waeber, Gerard, Kähönen, Mika, Lehtimäki, Terho, März, Winfried, Dehghan, Abbas, Franco, Oscar H., Uitterlinden, Andre G., Hofman, Albert, Taylor, Herman A., Chambers, John C., Kooner, Jaspal S., Fox, Caroline S., Hitzemann, Robert, Orwoll, Eric S., Pattaro, Cristian, Schlessinger, David, Köttgen, Anna, Snieder, Harold, Parsa, Afshin, Cohen, David M., UCL - SSS/IREC/NEFR - Pôle de Néphrologie, Böger, Carsten A., Gorski, Mathias, McMahon, Gearoid M., Xu, Huichun, Chang, Yen-Pei C., van der Most, Peter J., Navis, Gerjan, Nolte, Ilja M., de Borst, Martin H., Zhang, Weihua, Lehne, Benjamin, Loh, Marie, Tan, Sian-Tsung, Boerwinkle, Eric, Grams, Morgan E., Sekula, Peggy, Li, Man, Wilmot, Beth, Moon, James G., Scheet, Paul, Cucca, Francesco, Xiao, Xiangjun, Lyytikäinen, Leo-Pekka, Delgado, Graciela, Grammer, Tanja B., Kleber, Marcus E., Sedaghat, Sanaz, Rivadeneira, Fernando, Corre, Tanguy, Kutalik, Zoltan, Bergmann, Sven, Nielson, Carrie M., Srikanth, Priya, Teumer, Alexander, Müller-Nurasyid, Martina, Brockhaus, Anne Catharina, Pfeufer, Arne, Rathmann, Wolfgang, Peters, Annette, Matsumoto, Martha, de Andrade, Mariza, Atkinson, Elizabeth J., Robinson-Cohen, Cassianne, de Boer, Ian H., Hwang, Shih-Jen, Heid, Iris M., Gögele, Martin, Concas, Maria Pina, Tanaka, Toshiko, Bandinelli, Stefania, Nalls, Mike A., Singleton, Andrew, Tajuddin, Salman M., Adeyemo, Adebowale, Zhou, Jie, Doumatey, Ayo, McWeeney, Shannon, Murabito, Joanne, Franceschini, Nora, Flessner, Michael, Shlipak, Michael, Wilson, James G., Chen, Guanjie, Rotimi, Charles N., Zonderman, Alan B., Evans, Michele K., Ferrucci, Luigi, Devuyst, Olivier, Pirastu, Mario, Shuldiner, Alan, Hicks, Andrew A., Pramstaller, Peter Paul, Kestenbaum, Bryan, Kardia, Sharon L.R., Turner, Stephen T., Study, LifeLines Cohort, Briske, Tamara Ellefson, Gieger, Christian, Strauch, Konstantin, Meisinger, Christa, Meitinger, Thomas, Völker, Uwe, Nauck, Matthias, Völzke, Henry, Vollenweider, Peter, Bochud, Murielle, Waeber, Gerard, Kähönen, Mika, Lehtimäki, Terho, März, Winfried, Dehghan, Abbas, Franco, Oscar H., Uitterlinden, Andre G., Hofman, Albert, Taylor, Herman A., Chambers, John C., Kooner, Jaspal S., Fox, Caroline S., Hitzemann, Robert, Orwoll, Eric S., Pattaro, Cristian, Schlessinger, David, Köttgen, Anna, Snieder, Harold, Parsa, Afshin, and Cohen, David M.
- Abstract
Disorders of water balance, an excess or deficit of total body water relative to body electrolyte content, are common and ascertained by plasma hypo- or hypernatremia, respectively. We performed a two-stage genome-wide association study meta-analysis on plasma sodium concentration in 45,889 individuals of European descent (stage 1 discovery) and 17,637 additional individuals of European descent (stage 2 replication), and a transethnic meta-analysis of replicated single-nucleotide polymorphisms in 79,506 individuals (63,526 individuals of European descent, 8765 individuals of Asian Indian descent, and 7215 individuals of African descent). In stage 1, we identified eight loci associated with plasma sodium concentration at P<5.0 × 10-6 Of these, rs9980 at NFAT5 replicated in stage 2 meta-analysis (P=3.1 × 10-5), with combined stages 1 and 2 genome-wide significance of P=5.6 × 10-10 Transethnic meta-analysis further supported the association at rs9980 (P=5.9 × 10-12). Additionally, rs16846053 at SLC4A10 showed nominally, but not genome-wide, significant association in combined stages 1 and 2 meta-analysis (P=6.7 × 10-8). NFAT5 encodes a ubiquitously expressed transcription factor that coordinates the intracellular response to hypertonic stress but was not previously implicated in the regulation of systemic water balance. SLC4A10 encodes a sodium bicarbonate transporter with a brain-restricted expression pattern, and variant rs16846053 affects a putative intronic NFAT5 DNA binding motif. The lead variants for NFAT5 and SLC4A10 are cis expression quantitative trait loci in tissues of the central nervous system and relevant to transcriptional regulation. Thus, genetic variation in NFAT5 and SLC4A10 expression and function in the central nervous system may affect the regulation of systemic water balance.
- Published
- 2017
6. A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans
- Author
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Palmer, Nicholette D, McDonough, Caitrin W, Hicks, Pamela J, Roh, Bong H, Wing, Maria R, An, S Sandy, Hester, Jessica M, Cooke, Jessica N, Bostrom, Meredith A, Rudock, Megan E, Talbert, Matthew E, Lewis, Joshua P, DIAGRAM Consortium, MAGIC Investigators, Ferrara, Assiamira, Lu, Lingyi, Ziegler, Julie T, Sale, Michele M, Divers, Jasmin, Shriner, Daniel, Adeyemo, Adebowale, Rotimi, Charles N, Ng, Maggie CY, Langefeld, Carl D, Freedman, Barry I, Bowden, Donald W, Voight, Benjamin F, Scott, Laura J, Steinthorsdottir, Valgerdur, Morris, Andrew P, Dina, Christian, Welch, Ryan P, Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S, Thorleifsson, Gudmar, McCulloch, Laura J, Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J, Raychaudhuri, Soumya, McCarroll, Steve A, Langenberg, Claudia, Hofmann, Oliver M, Dupuis, Josée, Qi, Lu, Segrè, Ayellet V, Van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J, Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L, Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P, Charpentier, Guillaume, Chines, Peter S, Cornelis, Marilyn, Couper, David J, Crawford, Gabe, Doney, Alex SF, Elliott, Katherine S, Elliott, Amanda L, Erdos, Michael R, Fox, Caroline S, Franklin, Christopher S, Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J, Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U, Johnson, Paul RV, Jørgensen, Torben, Kao, Wen HL, Klopp, Norman, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M, Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, Midthjell, Kristian, Morken, Mario A, Narisu, Narisu, Nilsson, Peter, Owen, Katharine R, Payne, Felicity, Perry, John RB, Petersen, Ann-Kristin, Platou, Carl, Proença, Christine, Prokopenko, Inga, Rathmann, Wolfgang, Rayner, N William, Robertson, Neil R, Rocheleau, Ghislain, Roden, Michael, Sampson, Michael J, Saxena, Richa, Shields, Beverley M, Shrader, Peter, Sigurdsson, Gunnar, Sparsø, Thomas, Strassburger, Klaus, Stringham, Heather M, Sun, Qi, Swift, Amy J, Thorand, Barbara, Tichet, Jean, Tuomi, Tiinamaija, Van Dam, Rob M, Van Haeften, Timon W, Van Herpt, Thijs, Van Vliet-Ostaptchouk, Jana V, Walters, G Bragi, Weedon, Michael N, Wijmenga, Cisca, Witteman, Jacqueline, Bergman, Richard N, Cauchi, Stephane, Collins, Francis S, Gloyn, Anna L, Gyllensten, Ulf, Hansen, Torben, Hide, Winston A, Hitman, Graham A, Hofman, Albert, Hunter, David J, Hveem, Kristian, Laakso, Markku, Mohlke, Karen L, Morris, Andrew D, Palmer, Colin NA, Pramstaller, Peter P, Rudan, Igor, Sijbrands, Eric, Stein, Lincoln D, Tuomilehto, Jaakko, Uitterlinden, Andre, Walker, Mark, Wareham, Nicholas J, Watanabe, Richard M, Abecasis, Goncalo R, Boehm, Bernhard O, Campbell, Harry, Daly, Mark J, Hattersley, Andrew T, Hu, Frank B, Meigs, James B, Pankow, James S, Pedersen, Oluf, Wichmann, H-Erich, Barroso, Inês, Florez, Jose C, Frayling, Timothy M, Groop, Leif, Sladek, Rob, Thorsteinsdottir, Unnur, Wilson, James F, Illig, Thomas, Froguel, Philippe, Van Duijn, Cornelia M, Stefansson, Kari, Altshuler, David, Boehnke, Michael, McCarthy, Mark I, Soranzo, Nicole, Wheeler, Eleanor, Glazer, Nicole L, Bouatia-Naji, Nabila, Mägi, Reedik, Randall, Joshua, Johnson, Toby, Elliott, Paul, Rybin, Denis, Henneman, Peter, Dehghan, Abbas, Hottenga, Jouke Jan, Song, Kijoung, Goel, Anuj, Egan, Josephine M, Lajunen, Taina, Doney, Alex, Kanoni, Stavroula, Cavalcanti-Proença, Christine, Kumari, Meena, Timpson, Nicholas J, Zabena, Carina, Ingelsson, Erik, An, Ping, O'Connell, Jeffrey, Luan, Jian'an, Elliott, Amanda, McCarroll, Steven A, Roccasecca, Rosa Maria, Pattou, François, Sethupathy, Praveen, Ariyurek, Yavuz, Barter, Philip, Beilby, John P, Ben-Shlomo, Yoav, Bergmann, Sven, Bochud, Murielle, Bonnefond, Amélie, Borch-Johnsen, Knut, Böttcher, Yvonne, Brunner, Eric, Bumpstead, Suzannah J, Chen, Yii-Der Ida, Chines, Peter, Clarke, Robert, Coin, Lachlan JM, Cooper, Matthew N, Crisponi, Laura, Day, Ian NM, De Geus, Eco JC, Delplanque, Jerome, Fedson, Annette C, Fischer-Rosinsky, Antje, Forouhi, Nita G, Frants, Rune, Franzosi, Maria Grazia, Galan, Pilar, Goodarzi, Mark O, Graessler, Jürgen, Grundy, Scott, Gwilliam, Rhian, Hallmans, Göran, Hammond, Naomi, Han, Xijing, Hartikainen, Anna-Liisa, Hayward, Caroline, Heath, Simon C, Hercberg, Serge, Hicks, Andrew A, Hillman, David R, Hingorani, Aroon D, Hui, Jennie, Hung, Joe, Jula, Antti, Kaakinen, Marika, Kaprio, Jaakko, Kesaniemi, Y Antero, Kivimaki, Mika, Knight, Beatrice, Koskinen, Seppo, Kovacs, Peter, Kyvik, Kirsten Ohm, Lathrop, G Mark, Lawlor, Debbie A, Le Bacquer, Olivier, Lecoeur, Cécile, Li, Yun, Mahley, Robert, Mangino, Massimo, Manning, Alisa K, Martínez-Larrad, María Teresa, McAteer, Jarred B, McPherson, Ruth, Meisinger, Christa, Melzer, David, Meyre, David, Mitchell, Braxton D, Mukherjee, Sutapa, Naitza, Silvia, Neville, Matthew J, Oostra, Ben A, Orrù, Marco, Pakyz, Ruth, Paolisso, Giuseppe, Pattaro, Cristian, Pearson, Daniel, Peden, John F, Pedersen, Nancy L, Perola, Markus, Pfeiffer, Andreas FH, Pichler, Irene, Polasek, Ozren, Posthuma, Danielle, Potter, Simon C, Pouta, Anneli, Province, Michael A, Psaty, Bruce M, Rayner, Nigel W, Rice, Kenneth, Ripatti, Samuli, Rivadeneira, Fernando, Rolandsson, Olov, Sandbaek, Annelli, Sandhu, Manjinder, Sanna, Serena, Sayer, Avan Aihie, Scheet, Paul, Seedorf, Udo, Sharp, Stephen J, Shields, Beverley, Sijbrands, Eric JG, Silveira, Angela, Simpson, Laila, Singleton, Andrew, Smith, Nicholas L, Sovio, Ulla, Swift, Amy, Syddall, Holly, Syvänen, Ann-Christine, Tanaka, Toshiko, Tönjes, Anke, Uitterlinden, André G, Van Dijk, Ko Willems, Varma, Dhiraj, Visvikis-Siest, Sophie, Vitart, Veronique, Vogelzangs, Nicole, Waeber, Gérard, Wagner, Peter J, Walley, Andrew, Ward, Kim L, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Witteman, Jaqueline CM, Yarnell, John WG, Zelenika, Diana, Zethelius, Björn, Zhai, Guangju, Zhao, Jing Hua, Zillikens, M Carola, Borecki, Ingrid B, Loos, Ruth JF, Meneton, Pierre, Magnusson, Patrik KE, Nathan, David M, Williams, Gordon H, Silander, Kaisa, Salomaa, Veikko, Smith, George Davey, Bornstein, Stefan R, Schwarz, Peter, Spranger, Joachim, Karpe, Fredrik, Shuldiner, Alan R, Cooper, Cyrus, Dedoussis, George V, Serrano-Ríos, Manuel, Lind, Lars, Palmer, Lyle J, Franks, Paul W, Ebrahim, Shah, Marmot, Michael, Kao, WH Linda, Pramstaller, Peter Paul, Wright, Alan F, Stumvoll, Michael, Hamsten, Anders, Buchanan, Thomas A, Valle, Timo T, Rotter, Jerome I, Siscovick, David S, Penninx, Brenda WJH, Boomsma, Dorret I, Deloukas, Panos, Spector, Timothy D, Ferrucci, Luigi, Cao, Antonio, Scuteri, Angelo, Schlessinger, David, Uda, Manuela, Ruokonen, Aimo, Jarvelin, Marjo-Riitta, Waterworth, Dawn M, Vollenweider, Peter, Peltonen, Leena, Mooser, Vincent, Sladek, Robert, Center for Liver, Digestive and Metabolic Diseases (CLDM), Palmer, Nd, Mcdonough, Cw, Hicks, Pj, Roh, Bh, Wing, Mr, An, S, Hester, Jm, Cooke, Jn, Bostrom, Ma, Rudock, Me, Talbert, Me, Lewis, Jp, Diagram, Consortium, Magic, Investigator, Ferrara, A, Lu, L, Ziegler, Jt, Sale, Mm, Divers, J, Shriner, D, Adeyemo, A, Rotimi, Cn, Ng, Mc, Langefeld, Cd, Freedman, Bi, Bowden, Dw, Voight, Bf, Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Couper, Dj, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, J, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Johnson, T, Elliott, P, Rybin, D, Henneman, P, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Egan, Jm, Lajunen, T, Kanoni, S, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Frants, R, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hicks, Aa, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Manning, Ak, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Oostra, Ba, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Perola, M, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Psaty, Bm, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tanaka, T, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Borecki, Ib, Loos, Rj, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Salomaa, V, Smith, Gd, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Dedoussis, Gv, Serrano Ríos, M, Lind, L, Palmer, Lj, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Buchanan, Ta, Valle, Tt, Rotter, Ji, Siscovick, D, Penninx, Bw, Boomsma, Di, Deloukas, P, Spector, Td, Ferrucci, L, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Waterworth, Dm, Vollenweider, P, Peltonen, L, Mooser, V, Sladek, R., Medical Research Council (MRC), Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Langenberg, Claudia [0000-0002-5017-7344], Griffin, Simon [0000-0002-2157-4797], Wareham, Nicholas [0000-0003-1422-2993], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Apollo - University of Cambridge Repository, DIAGRAM Consortium, MAGIC Investigators, Johnson, T., Bergman, S., Bochud, M., Waeber, G., and Vollenweider, P.
- Subjects
Netherlands Twin Register (NTR) ,Male ,Adult ,African Americans/genetics ,Aged ,Case-Control Studies ,Cohort Studies ,Diabetes Mellitus, Type 2/ethnology ,Diabetes Mellitus, Type 2/genetics ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Meta-Analysis as Topic ,Middle Aged ,Polymorphism, Single Nucleotide ,Validation Studies as Topic ,Medicin och hälsovetenskap ,Linkage disequilibrium ,Genetic Screens ,endocrine system diseases ,lcsh:Medicine ,Genome-wide association study ,Medical and Health Sciences ,0302 clinical medicine ,Endocrinology ,Genome Sequencing ,lcsh:Science ,Medicine(all) ,Genetics ,African Americans ,0303 health sciences ,education.field_of_study ,INSULIN-RESISTANCE ,Multidisciplinary ,Agricultural and Biological Sciences(all) ,LARGE-SCALE ASSOCIATION ,STAGE RENAL-DISEASE ,COMMON VARIANTS ,Genomics ,Medicine ,Research Article ,SUSCEPTIBILITY LOCI ,General Science & Technology ,Population ,Single-nucleotide polymorphism ,Biology ,DIAGRAM Consortium ,03 medical and health sciences ,MAGIC Investigators ,SDG 3 - Good Health and Well-being ,Genetic linkage ,MD Multidisciplinary ,Genome-Wide Association Studies ,SNP ,ddc:610 ,education ,Genotyping ,030304 developmental biology ,Diabetic Endocrinology ,LINKAGE ANALYSIS ,Biochemistry, Genetics and Molecular Biology(all) ,lcsh:R ,TCF7L2 GENE ,Case-control study ,Computational Biology ,nutritional and metabolic diseases ,Human Genetics ,Diabetes Mellitus Type 2 ,Stage renal-disease ,large-scale association ,Susceptibility loci ,Insulin-resistance ,Fasting glucose ,Tissue factor ,Homeodomain protein ,Linkage analysis ,Common variants ,TCF7L2 gene ,Black or African American ,Diabetes Mellitus, Type 2 ,TISSUE FACTOR ,Genetics of Disease ,HOMEODOMAIN PROTEIN ,Genetic Polymorphism ,lcsh:Q ,Genome Expression Analysis ,030217 neurology & neurosurgery ,Population Genetics ,FASTING GLUCOSE - Abstract
African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P
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- 2012
7. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
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Dupuis, Josée, Langenberg, Claudia, Prokopenko, Inga, Saxena, Richa, Soranzo, Nicole, Jackson, Anne U, Wheeler, Eleanor, Glazer, Nicole L, Bouatia-Naji, Nabila, Gloyn, Anna L, Lindgren, Cecilia M, Mägi, Reedik, Morris, Andrew P, Randall, Joshua, Johnson, Toby, Elliott, Paul, Rybin, Denis, Thorleifsson, Gudmar, Steinthorsdottir, Valgerdur, Henneman, Peter, Grallert, Harald, Dehghan, Abbas, Hottenga, Jouke Jan, Franklin, Christopher S, Navarro, Pau, Song, Kijoung, Goel, Anuj, Perry, John R B, Egan, Josephine M, Lajunen, Taina, Grarup, Niels, Sparsø, Thomas, Doney, Alex, Voight, Benjamin F, Stringham, Heather M, Li, Man, Kanoni, Stavroula, Shrader, Peter, Cavalcanti-Proença, Christine, Kumari, Meena, Qi, Lu, Timpson, Nicholas J, Gieger, Christian, Zabena, Carina, Rocheleau, Ghislain, Ingelsson, Erik, An, Ping, O'Connell, Jeffrey, Luan, Jian'an, Elliott, Amanda, McCarroll, Steven A, Payne, Felicity, Roccasecca, Rosa Maria, Pattou, François, Sethupathy, Praveen, Ardlie, Kristin, Ariyurek, Yavuz, Balkau, Beverley, Barter, Philip, Beilby, John P, Ben-Shlomo, Yoav, Benediktsson, Rafn, Bennett, Amanda J, Bergmann, Sven, Bochud, Murielle, Boerwinkle, Eric, Bonnefond, Amélie, Bonnycastle, Lori L, Borch-Johnsen, Knut, Böttcher, Yvonne, Brunner, Eric, Bumpstead, Suzannah J, Charpentier, Guillaume, Chen, Yii-Der Ida, Chines, Peter, Clarke, Robert, Coin, Lachlan J M, Cooper, Matthew N, Cornelis, Marilyn, Crawford, Gabe, Crisponi, Laura, Day, Ian N M, de Geus, Eco J C, Delplanque, Jerome, Dina, Christian, Erdos, Michael R, Fedson, Annette C, Fischer-Rosinsky, Antje, Forouhi, Nita G, Fox, Caroline S, Frants, Rune, Franzosi, Maria Grazia, Galan, Pilar, Goodarzi, Mark O, Graessler, Jürgen, Groves, Christopher J, Grundy, Scott, Gwilliam, Rhian, Gyllensten, Ulf, Hadjadj, Samy, Hallmans, Göran, Hammond, Naomi, Han, Xijing, Hartikainen, Anna-Liisa, Hassanali, Neelam, Hayward, Caroline, Heath, Simon C, Hercberg, Serge, Herder, Christian, Hicks, Andrew A, Hillman, David R, Hingorani, Aroon D, Hofman, Albert, Hui, Jennie, Hung, Joe, Isomaa, Bo, Johnson, Paul R V, Jørgensen, Torben, Jula, Antti, Kaakinen, Marika, Kaprio, Jaakko, Kesaniemi, Y Antero, Kivimaki, Mika, Knight, Beatrice, Koskinen, Seppo, Kovacs, Peter, Kyvik, Kirsten Ohm, Lathrop, G Mark, Lawlor, Debbie A, Le Bacquer, Olivier, Lecoeur, Cécile, Li, Yun, Lyssenko, Valeriya, Mahley, Robert, Mangino, Massimo, Manning, Alisa K, Martínez-Larrad, María Teresa, McAteer, Jarred B, McCulloch, Laura J, McPherson, Ruth, Meisinger, Christa, Melzer, David, Meyre, David, Mitchell, Braxton D, Morken, Mario A, Mukherjee, Sutapa, Naitza, Silvia, Narisu, Narisu, Neville, Matthew J, Oostra, Ben A, Orrù, Marco, Pakyz, Ruth, Palmer, Colin N A, Paolisso, Giuseppe, Pattaro, Cristian, Pearson, Daniel, Peden, John F, Pedersen, Nancy L, Perola, Markus, Pfeiffer, Andreas F H, Pichler, Irene, Polasek, Ozren, Posthuma, Danielle, Potter, Simon C, Pouta, Anneli, Province, Michael A, Psaty, Bruce M, Rathmann, Wolfgang, Rayner, Nigel W, Rice, Kenneth, Ripatti, Samuli, Rivadeneira, Fernando, Roden, Michael, Rolandsson, Olov, Sandbaek, Annelli, Sandhu, Manjinder, Sanna, Serena, Sayer, Avan Aihie, Scheet, Paul, Scott, Laura J, Seedorf, Udo, Sharp, Stephen J, Shields, Beverley, Sigurethsson, Gunnar, Sijbrands, Eric J G, Silveira, Angela, Simpson, Laila, Singleton, Andrew, Smith, Nicholas L, Sovio, Ulla, Swift, Amy, Syddall, Holly, Syvänen, Ann-Christine, Tanaka, Toshiko, Thorand, Barbara, Tichet, Jean, Tönjes, Anke, Tuomi, Tiinamaija, Uitterlinden, André G, van Dijk, Ko Willems, van Hoek, Mandy, Varma, Dhiraj, Visvikis-Siest, Sophie, Vitart, Veronique, Vogelzangs, Nicole, Waeber, Gérard, Wagner, Peter J, Walley, Andrew, Walters, G Bragi, Ward, Kim L, Watkins, Hugh, Weedon, Michael N, Wild, Sarah H, Willemsen, Gonneke, Witteman, Jaqueline C M, Yarnell, John W G, Zeggini, Eleftheria, Zelenika, Diana, Zethelius, Björn, Zhai, Guangju, Zhao, Jing Hua, Zillikens, M Carola, Borecki, Ingrid B, Loos, Ruth J F, Meneton, Pierre, Magnusson, Patrik K E, Nathan, David M, Williams, Gordon H, Hattersley, Andrew T, Silander, Kaisa, Salomaa, Veikko, Smith, George Davey, Bornstein, Stefan R, Schwarz, Peter, Spranger, Joachim, Karpe, Fredrik, Shuldiner, Alan R, Cooper, Cyrus, Dedoussis, George V, Serrano-Ríos, Manuel, Morris, Andrew D, Lind, Lars, Palmer, Lyle J, Hu, Frank B, Franks, Paul W, Ebrahim, Shah, Marmot, Michael, Kao, W H Linda, Pankow, James S, Sampson, Michael J, Kuusisto, Johanna, Laakso, Markku, Hansen, Torben, Pedersen, Oluf, Pramstaller, Peter Paul, Wichmann, H Erich, Illig, Thomas, Rudan, Igor, Wright, Alan F, Stumvoll, Michael, Campbell, Harry, Wilson, James F, Bergman, Richard N, Buchanan, Thomas A, Collins, Francis S, Mohlke, Karen L, Tuomilehto, Jaakko, Valle, Timo T, Altshuler, David, Rotter, Jerome I, Siscovick, David S, Penninx, Brenda W J H, Boomsma, Dorret I, Deloukas, Panos, Spector, Timothy D, Frayling, Timothy M, Ferrucci, Luigi, Kong, Augustine, Thorsteinsdottir, Unnur, Stefansson, Kari, van Duijn, Cornelia M, Aulchenko, Yurii S, Cao, Antonio, Scuteri, Angelo, Schlessinger, David, Uda, Manuela, Ruokonen, Aimo, Jarvelin, Marjo-Riitta, Waterworth, Dawn M, Vollenweider, Peter, Peltonen, Leena, Mooser, Vincent, Abecasis, Goncalo R, Wareham, Nicholas J, Sladek, Robert, Froguel, Philippe, Watanabe, Richard M, Meigs, James B, Groop, Leif, Boehnke, Michael, McCarthy, Mark I, Florez, Jose C, Barroso, Inês, Dupuis, Josée, Langenberg, Claudia, Prokopenko, Inga, Saxena, Richa, Soranzo, Nicole, Jackson, Anne U, Wheeler, Eleanor, Glazer, Nicole L, Bouatia-Naji, Nabila, Gloyn, Anna L, Lindgren, Cecilia M, Mägi, Reedik, Morris, Andrew P, Randall, Joshua, Johnson, Toby, Elliott, Paul, Rybin, Denis, Thorleifsson, Gudmar, Steinthorsdottir, Valgerdur, Henneman, Peter, Grallert, Harald, Dehghan, Abbas, Hottenga, Jouke Jan, Franklin, Christopher S, Navarro, Pau, Song, Kijoung, Goel, Anuj, Perry, John R B, Egan, Josephine M, Lajunen, Taina, Grarup, Niels, Sparsø, Thomas, Doney, Alex, Voight, Benjamin F, Stringham, Heather M, Li, Man, Kanoni, Stavroula, Shrader, Peter, Cavalcanti-Proença, Christine, Kumari, Meena, Qi, Lu, Timpson, Nicholas J, Gieger, Christian, Zabena, Carina, Rocheleau, Ghislain, Ingelsson, Erik, An, Ping, O'Connell, Jeffrey, Luan, Jian'an, Elliott, Amanda, McCarroll, Steven A, Payne, Felicity, Roccasecca, Rosa Maria, Pattou, François, Sethupathy, Praveen, Ardlie, Kristin, Ariyurek, Yavuz, Balkau, Beverley, Barter, Philip, Beilby, John P, Ben-Shlomo, Yoav, Benediktsson, Rafn, Bennett, Amanda J, Bergmann, Sven, Bochud, Murielle, Boerwinkle, Eric, Bonnefond, Amélie, Bonnycastle, Lori L, Borch-Johnsen, Knut, Böttcher, Yvonne, Brunner, Eric, Bumpstead, Suzannah J, Charpentier, Guillaume, Chen, Yii-Der Ida, Chines, Peter, Clarke, Robert, Coin, Lachlan J M, Cooper, Matthew N, Cornelis, Marilyn, Crawford, Gabe, Crisponi, Laura, Day, Ian N M, de Geus, Eco J C, Delplanque, Jerome, Dina, Christian, Erdos, Michael R, Fedson, Annette C, Fischer-Rosinsky, Antje, Forouhi, Nita G, Fox, Caroline S, Frants, Rune, Franzosi, Maria Grazia, Galan, Pilar, Goodarzi, Mark O, Graessler, Jürgen, Groves, Christopher J, Grundy, Scott, Gwilliam, Rhian, Gyllensten, Ulf, Hadjadj, Samy, Hallmans, Göran, Hammond, Naomi, Han, Xijing, Hartikainen, Anna-Liisa, Hassanali, Neelam, Hayward, Caroline, Heath, Simon C, Hercberg, Serge, Herder, Christian, Hicks, Andrew A, Hillman, David R, Hingorani, Aroon D, Hofman, Albert, Hui, Jennie, Hung, Joe, Isomaa, Bo, Johnson, Paul R V, Jørgensen, Torben, Jula, Antti, Kaakinen, Marika, Kaprio, Jaakko, Kesaniemi, Y Antero, Kivimaki, Mika, Knight, Beatrice, Koskinen, Seppo, Kovacs, Peter, Kyvik, Kirsten Ohm, Lathrop, G Mark, Lawlor, Debbie A, Le Bacquer, Olivier, Lecoeur, Cécile, Li, Yun, Lyssenko, Valeriya, Mahley, Robert, Mangino, Massimo, Manning, Alisa K, Martínez-Larrad, María Teresa, McAteer, Jarred B, McCulloch, Laura J, McPherson, Ruth, Meisinger, Christa, Melzer, David, Meyre, David, Mitchell, Braxton D, Morken, Mario A, Mukherjee, Sutapa, Naitza, Silvia, Narisu, Narisu, Neville, Matthew J, Oostra, Ben A, Orrù, Marco, Pakyz, Ruth, Palmer, Colin N A, Paolisso, Giuseppe, Pattaro, Cristian, Pearson, Daniel, Peden, John F, Pedersen, Nancy L, Perola, Markus, Pfeiffer, Andreas F H, Pichler, Irene, Polasek, Ozren, Posthuma, Danielle, Potter, Simon C, Pouta, Anneli, Province, Michael A, Psaty, Bruce M, Rathmann, Wolfgang, Rayner, Nigel W, Rice, Kenneth, Ripatti, Samuli, Rivadeneira, Fernando, Roden, Michael, Rolandsson, Olov, Sandbaek, Annelli, Sandhu, Manjinder, Sanna, Serena, Sayer, Avan Aihie, Scheet, Paul, Scott, Laura J, Seedorf, Udo, Sharp, Stephen J, Shields, Beverley, Sigurethsson, Gunnar, Sijbrands, Eric J G, Silveira, Angela, Simpson, Laila, Singleton, Andrew, Smith, Nicholas L, Sovio, Ulla, Swift, Amy, Syddall, Holly, Syvänen, Ann-Christine, Tanaka, Toshiko, Thorand, Barbara, Tichet, Jean, Tönjes, Anke, Tuomi, Tiinamaija, Uitterlinden, André G, van Dijk, Ko Willems, van Hoek, Mandy, Varma, Dhiraj, Visvikis-Siest, Sophie, Vitart, Veronique, Vogelzangs, Nicole, Waeber, Gérard, Wagner, Peter J, Walley, Andrew, Walters, G Bragi, Ward, Kim L, Watkins, Hugh, Weedon, Michael N, Wild, Sarah H, Willemsen, Gonneke, Witteman, Jaqueline C M, Yarnell, John W G, Zeggini, Eleftheria, Zelenika, Diana, Zethelius, Björn, Zhai, Guangju, Zhao, Jing Hua, Zillikens, M Carola, Borecki, Ingrid B, Loos, Ruth J F, Meneton, Pierre, Magnusson, Patrik K E, Nathan, David M, Williams, Gordon H, Hattersley, Andrew T, Silander, Kaisa, Salomaa, Veikko, Smith, George Davey, Bornstein, Stefan R, Schwarz, Peter, Spranger, Joachim, Karpe, Fredrik, Shuldiner, Alan R, Cooper, Cyrus, Dedoussis, George V, Serrano-Ríos, Manuel, Morris, Andrew D, Lind, Lars, Palmer, Lyle J, Hu, Frank B, Franks, Paul W, Ebrahim, Shah, Marmot, Michael, Kao, W H Linda, Pankow, James S, Sampson, Michael J, Kuusisto, Johanna, Laakso, Markku, Hansen, Torben, Pedersen, Oluf, Pramstaller, Peter Paul, Wichmann, H Erich, Illig, Thomas, Rudan, Igor, Wright, Alan F, Stumvoll, Michael, Campbell, Harry, Wilson, James F, Bergman, Richard N, Buchanan, Thomas A, Collins, Francis S, Mohlke, Karen L, Tuomilehto, Jaakko, Valle, Timo T, Altshuler, David, Rotter, Jerome I, Siscovick, David S, Penninx, Brenda W J H, Boomsma, Dorret I, Deloukas, Panos, Spector, Timothy D, Frayling, Timothy M, Ferrucci, Luigi, Kong, Augustine, Thorsteinsdottir, Unnur, Stefansson, Kari, van Duijn, Cornelia M, Aulchenko, Yurii S, Cao, Antonio, Scuteri, Angelo, Schlessinger, David, Uda, Manuela, Ruokonen, Aimo, Jarvelin, Marjo-Riitta, Waterworth, Dawn M, Vollenweider, Peter, Peltonen, Leena, Mooser, Vincent, Abecasis, Goncalo R, Wareham, Nicholas J, Sladek, Robert, Froguel, Philippe, Watanabe, Richard M, Meigs, James B, Groop, Leif, Boehnke, Michael, McCarthy, Mark I, Florez, Jose C, and Barroso, Inês
- Abstract
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
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- 2010
- Full Text
- View/download PDF
8. NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality
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Carsten A. Böger, Mathias Gorski, Gearoid M. McMahon, Huichun Xu, Yen-Pei C. Chang, Peter J. van der Most, Gerjan Navis, Ilja M. Nolte, Martin H. de Borst, Weihua Zhang, Benjamin Lehne, Marie Loh, Sian-Tsung Tan, Eric Boerwinkle, Morgan E. Grams, Peggy Sekula, Man Li, Beth Wilmot, James G. Moon, Paul Scheet, Francesco Cucca, Xiangjun Xiao, Leo-Pekka Lyytikäinen, Graciela Delgado, Tanja B. Grammer, Marcus E. Kleber, Sanaz Sedaghat, Fernando Rivadeneira, Tanguy Corre, Zoltan Kutalik, Sven Bergmann, Carrie M. Nielson, Priya Srikanth, Alexander Teumer, Martina Müller-Nurasyid, Anne Catharina Brockhaus, Arne Pfeufer, Wolfgang Rathmann, Annette Peters, Martha Matsumoto, Mariza de Andrade, Elizabeth J. Atkinson, Cassianne Robinson-Cohen, Ian H. de Boer, Shih-Jen Hwang, Iris M. Heid, Martin Gögele, Maria Pina Concas, Toshiko Tanaka, Stefania Bandinelli, Mike A. Nalls, Andrew Singleton, Salman M. Tajuddin, Adebowale Adeyemo, Jie Zhou, Ayo Doumatey, Shannon McWeeney, Joanne Murabito, Nora Franceschini, Michael Flessner, Michael Shlipak, James G. Wilson, Guanjie Chen, Charles N. Rotimi, Alan B. Zonderman, Michele K. Evans, Luigi Ferrucci, Olivier Devuyst, Mario Pirastu, Alan Shuldiner, Andrew A. Hicks, Peter Paul Pramstaller, Bryan Kestenbaum, Sharon L.R. Kardia, Stephen T. Turner, LifeLines Cohort Study, Tamara Ellefson Briske, Christian Gieger, Konstantin Strauch, Christa Meisinger, Thomas Meitinger, Uwe Völker, Matthias Nauck, Henry Völzke, Peter Vollenweider, Murielle Bochud, Gerard Waeber, Mika Kähönen, Terho Lehtimäki, Winfried März, Abbas Dehghan, Oscar H. Franco, Andre G. Uitterlinden, Albert Hofman, Herman A. Taylor, John C. Chambers, Jaspal S. Kooner, Caroline S. Fox, Robert Hitzemann, Eric S. Orwoll, Cristian Pattaro, David Schlessinger, Anna Köttgen, Harold Snieder, Afshin Parsa, David M. Cohen, Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Life Course Epidemiology (LCE), Value, Affordability and Sustainability (VALUE), Groningen Institute for Organ Transplantation (GIOT), Böger, Carsten A., Gorski, Mathia, Mcmahon, Gearoid M., Xu, Huichun, Chang, Yen Pei C., Van Der Most, Peter J., Navis, Gerjan, Nolte, Ilja M., De Borst, Martin H., Zhang, Weihua, Lehne, Benjamin, Loh, Marie, Tan, Sian Tsung, Boerwinkle, Eric, Grams, Morgan E., Sekula, Peggy, Li, Man, Wilmot, Beth, Moon, James G., Scheet, Paul, Cucca, Francesco, Xiao, Xiangjun, Lyytikäinen, Leo Pekka, Delgado, Graciela, Grammer, Tanja B., Kleber, Marcus E., Sedaghat, Sanaz, Rivadeneira, Fernando, Corre, Tanguy, Kutalik, Zoltan, Bergmann, Sven, Nielson, Carrie M., Srikanth, Priya, Teumer, Alexander, Müller Nurasyid, Martina, Brockhaus, Anne Catharina, Pfeufer, Arne, Rathmann, Wolfgang, Peters, Annette, Matsumoto, Martha, De Andrade, Mariza, Atkinson, Elizabeth J., Robinson Cohen, Cassianne, De Boer, Ian H., Hwang, Shih Jen, Heid, Iris M., Gögele, Martin, Concas, MARIA PINA, Tanaka, Toshiko, Bandinelli, Stefania, Nalls, Mike A., Singleton, Andrew, Tajuddin, Salman M., Adeyemo, Adebowale, Zhou, Jie, Doumatey, Ayo, Mcweeney, Shannon, Murabito, Joanne, Franceschini, Nora, Flessner, Michael, Shlipak, Michael, Wilson, James G., Chen, Guanjie, Rotimi, Charles N., Zonderman, Alan B., Evans, Michele K., Ferrucci, Luigi, Devuyst, Olivier, Pirastu, Mario, Shuldiner, Alan, Hicks, Andrew A., Pramstaller, Peter Paul, Kestenbaum, Bryan, Kardia, Sharon L. R., Turner, Stephen T., Study, Lifelines Cohort, Briske, Tamara Ellefson, Gieger, Christian, Strauch, Konstantin, Meisinger, Christa, Meitinger, Thoma, Völker, Uwe, Nauck, Matthia, Völzke, Henry, Vollenweider, Peter, Bochud, Murielle, Waeber, Gerard, Kähönen, Mika, Lehtimäki, Terho, März, Winfried, Dehghan, Abba, Franco, Oscar H., Uitterlinden, Andre G., Hofman, Albert, Taylor, Herman A., Chambers, John C., Kooner, Jaspal S., Fox, Caroline S., Hitzemann, Robert, Orwoll, Eric S., Pattaro, Cristian, Schlessinger, David, Köttgen, Anna, Snieder, Harold, Parsa, Afshin, and Cohen, David M.
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0301 basic medicine ,medicine.medical_specialty ,hyponatremia ,Body water ,Water-Electrolyte Imbalance ,PROTEIN ,human genetics ,Genome-wide association study ,Biology ,03 medical and health sciences ,Plasma ,NFAT5 ,Internal medicine ,Gene expression ,Genetic variation ,Transcriptional regulation ,medicine ,Humans ,human genetic ,CELL-TYPES ,GENE-EXPRESSION ,Genetics ,IDENTIFICATION ,hypernatremia ,Sodium-Bicarbonate Symporter ,Sodium-Bicarbonate Symporters ,Sodium ,PRIMARY-CARE ,1103 Clinical Sciences ,General Medicine ,Urology & Nephrology ,water-electrolyte balance ,Plasma osmolality ,Human Genetics ,Hypernatremia ,Hyponatremia ,Water-electrolyte Balance ,030104 developmental biology ,Endocrinology ,Basic Research ,NEPHROGENIC DIABETES-INSIPIDUS ,Genome-Wide Association Study ,Genetic Loci ,Nephrology ,Expression quantitative trait loci ,TRANSCRIPTION FACTOR-BINDING ,INAPPROPRIATE ANTIDIURESIS ,INTRONIC ENHANCERS ,Human - Abstract
Disorders of water balance, an excess or deficit of total body water relative to body electrolyte content, are common and ascertained by plasma hypo- or hypernatremia, respectively. We performed a two-stage genome-wide association study meta-analysis on plasma sodium concentration in 45,889 individuals of European descent (stage 1 discovery) and 17,637 additional individuals of European descent (stage 2 replication), and a transethnic meta-analysis of replicated single-nucleotide polymorphisms in 79,506 individuals (63,526 individuals of European descent, 8765 individuals of Asian Indian descent, and 7215 individuals of African descent). In stage 1, we identified eight loci associated with plasma sodium concentration at P-6. Of these, rs9980 at NFAT5 replicated in stage 2 meta-analysis (P=3.1 3 x 10-5), with combined stages 1 and 2 genomewide significance of P=5.6 x 10-10. Transethnic meta-analysis further supported the association at rs9980 (P=5.9 x 10-12). Additionally, rs16846053 at SLC4A10 showed nominally, but not genome-wide, significant association in combined stages 1 and 2 meta-analysis (P=6.7 x 10-8). NFAT5 encodes a ubiquitously expressed transcription factor that coordinates the intracellular response to hypertonic stress but was not previously implicated in the regulation of systemic water balance. SLC4A10 encodes a sodium bicarbonate transporter with a brain-restricted expression pattern, and variant rs16846053 affects a putative intronic NFAT5 DNA binding motif. The lead variants for NFAT5 and SLC4A10 are cis expression quantitative trait loci in tissues of the central nervous systemand relevant to transcriptional regulation. Thus, genetic variation in NFAT5 and SLC4A10 expression and function in the central nervous system may affect the regulation of systemic water balance.
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- 2017
9. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.
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Teumer A, Tin A, Sorice R, Gorski M, Yeo NC, Chu AY, Li M, Li Y, Mijatovic V, Ko YA, Taliun D, Luciani A, Chen MH, Yang Q, Foster MC, Olden M, Hiraki LT, Tayo BO, Fuchsberger C, Dieffenbach AK, Shuldiner AR, Smith AV, Zappa AM, Lupo A, Kollerits B, Ponte B, Stengel B, Krämer BK, Paulweber B, Mitchell BD, Hayward C, Helmer C, Meisinger C, Gieger C, Shaffer CM, Müller C, Langenberg C, Ackermann D, Siscovick D, Boerwinkle E, Kronenberg F, Ehret GB, Homuth G, Waeber G, Navis G, Gambaro G, Malerba G, Eiriksdottir G, Li G, Wichmann HE, Grallert H, Wallaschofski H, Völzke H, Brenner H, Kramer H, Mateo Leach I, Rudan I, Hillege HL, Beckmann JS, Lambert JC, Luan J, Zhao JH, Chalmers J, Coresh J, Denny JC, Butterbach K, Launer LJ, Ferrucci L, Kedenko L, Haun M, Metzger M, Woodward M, Hoffman MJ, Nauck M, Waldenberger M, Pruijm M, Bochud M, Rheinberger M, Verweij N, Wareham NJ, Endlich N, Soranzo N, Polasek O, van der Harst P, Pramstaller PP, Vollenweider P, Wild PS, Gansevoort RT, Rettig R, Biffar R, Carroll RJ, Katz R, Loos RJ, Hwang SJ, Coassin S, Bergmann S, Rosas SE, Stracke S, Harris TB, Corre T, Zeller T, Illig T, Aspelund T, Tanaka T, Lendeckel U, Völker U, Gudnason V, Chouraki V, Koenig W, Kutalik Z, O'Connell JR, Parsa A, Heid IM, Paterson AD, de Boer IH, Devuyst O, Lazar J, Endlich K, Susztak K, Tremblay J, Hamet P, Jacob HJ, Böger CA, Fox CS, Pattaro C, and Köttgen A
- Subjects
- Adult, Aged, Albuminuria etiology, Animals, Cathepsin C genetics, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2 complications, Diabetic Nephropathies etiology, Female, Gene Knockout Techniques, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney metabolism, Male, Middle Aged, Polymorphism, Single Nucleotide, Rats, Receptors, Cell Surface genetics, Sulfotransferases genetics, rab GTP-Binding Proteins genetics, rab GTP-Binding Proteins metabolism, Albuminuria genetics, Diabetes Mellitus, Type 2 genetics, Diabetic Nephropathies genetics, Kidney Tubules metabolism
- Abstract
Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
- Published
- 2016
- Full Text
- View/download PDF
10. A genome-wide association search for type 2 diabetes genes in African Americans.
- Author
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Palmer ND, McDonough CW, Hicks PJ, Roh BH, Wing MR, An SS, Hester JM, Cooke JN, Bostrom MA, Rudock ME, Talbert ME, Lewis JP, Ferrara A, Lu L, Ziegler JT, Sale MM, Divers J, Shriner D, Adeyemo A, Rotimi CN, Ng MC, Langefeld CD, Freedman BI, Bowden DW, Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, Segrè AV, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet-Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Altshuler D, Boehnke M, McCarthy MI, Soranzo N, Wheeler E, Glazer NL, Bouatia-Naji N, Mägi R, Randall J, Johnson T, Elliott P, Rybin D, Henneman P, Dehghan A, Hottenga JJ, Song K, Goel A, Egan JM, Lajunen T, Doney A, Kanoni S, Cavalcanti-Proença C, Kumari M, Timpson NJ, Zabena C, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, McCarroll SA, Roccasecca RM, Pattou F, Sethupathy P, Ariyurek Y, Barter P, Beilby JP, Ben-Shlomo Y, Bergmann S, Bochud M, Bonnefond A, Borch-Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Crisponi L, Day IN, de Geus EJ, Delplanque J, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Grundy S, Gwilliam R, Hallmans G, Hammond N, Han X, Hartikainen AL, Hayward C, Heath SC, Hercberg S, Hicks AA, Hillman DR, Hingorani AD, Hui J, Hung J, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Mahley R, Mangino M, Manning AK, Martínez-Larrad MT, McAteer JB, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Mukherjee S, Naitza S, Neville MJ, Oostra BA, Orrù M, Pakyz R, Paolisso G, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rayner NW, Rice K, Ripatti S, Rivadeneira F, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Seedorf U, Sharp SJ, Shields B, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Tönjes A, Uitterlinden AG, van Dijk KW, Varma D, Visvikis-Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Ward KL, Watkins H, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano-Ríos M, Lind L, Palmer LJ, Franks PW, Ebrahim S, Marmot M, Kao WH, Pramstaller PP, Wright AF, Stumvoll M, Hamsten A, Buchanan TA, Valle TT, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Ferrucci L, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, and Sladek R
- Subjects
- Adult, Aged, Case-Control Studies, Cohort Studies, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Validation Studies as Topic, Black or African American genetics, Diabetes Mellitus, Type 2 ethnology, Diabetes Mellitus, Type 2 genetics, Genome-Wide Association Study
- Abstract
African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
- Published
- 2012
- Full Text
- View/download PDF
11. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
- Author
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Dastani Z, Hivert MF, Timpson N, Perry JR, Yuan X, Scott RA, Henneman P, Heid IM, Kizer JR, Lyytikäinen LP, Fuchsberger C, Tanaka T, Morris AP, Small K, Isaacs A, Beekman M, Coassin S, Lohman K, Qi L, Kanoni S, Pankow JS, Uh HW, Wu Y, Bidulescu A, Rasmussen-Torvik LJ, Greenwood CM, Ladouceur M, Grimsby J, Manning AK, Liu CT, Kooner J, Mooser VE, Vollenweider P, Kapur KA, Chambers J, Wareham NJ, Langenberg C, Frants R, Willems-Vandijk K, Oostra BA, Willems SM, Lamina C, Winkler TW, Psaty BM, Tracy RP, Brody J, Chen I, Viikari J, Kähönen M, Pramstaller PP, Evans DM, St Pourcain B, Sattar N, Wood AR, Bandinelli S, Carlson OD, Egan JM, Böhringer S, van Heemst D, Kedenko L, Kristiansson K, Nuotio ML, Loo BM, Harris T, Garcia M, Kanaya A, Haun M, Klopp N, Wichmann HE, Deloukas P, Katsareli E, Couper DJ, Duncan BB, Kloppenburg M, Adair LS, Borja JB, Wilson JG, Musani S, Guo X, Johnson T, Semple R, Teslovich TM, Allison MA, Redline S, Buxbaum SG, Mohlke KL, Meulenbelt I, Ballantyne CM, Dedoussis GV, Hu FB, Liu Y, Paulweber B, Spector TD, Slagboom PE, Ferrucci L, Jula A, Perola M, Raitakari O, Florez JC, Salomaa V, Eriksson JG, Frayling TM, Hicks AA, Lehtimäki T, Smith GD, Siscovick DS, Kronenberg F, van Duijn C, Loos RJ, Waterworth DM, Meigs JB, Dupuis J, Richards JB, Voight BF, Scott LJ, Steinthorsdottir V, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Hofmann OM, Segrè AV, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet-Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Morris AD, Palmer CN, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Pedersen O, Barroso I, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Altshuler D, Boehnke M, McCarthy MI, Soranzo N, Wheeler E, Glazer NL, Bouatia-Naji N, Mägi R, Randall J, Elliott P, Rybin D, Dehghan A, Hottenga JJ, Song K, Goel A, Lajunen T, Doney A, Cavalcanti-Proença C, Kumari M, Timpson NJ, Zabena C, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, McCarroll SA, Roccasecca RM, Pattou F, Sethupathy P, Ariyurek Y, Barter P, Beilby JP, Ben-Shlomo Y, Bergmann S, Bochud M, Bonnefond A, Borch-Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Crisponi L, Day IN, de Geus EJ, Delplanque J, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Grundy S, Gwilliam R, Hallmans G, Hammond N, Han X, Hartikainen AL, Hayward C, Heath SC, Hercberg S, Hillman DR, Hingorani AD, Hui J, Hung J, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Mahley R, Mangino M, Martínez-Larrad MT, McAteer JB, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Mukherjee S, Naitza S, Neville MJ, Orrù M, Pakyz R, Paolisso G, Pattaro C, Pearson D, Peden JF, Pedersen NL, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Rayner NW, Rice K, Ripatti S, Rivadeneira F, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Seedorf U, Sharp SJ, Shields B, Sigurðsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tönjes A, Uitterlinden AG, van Dijk KW, Varma D, Visvikis-Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Ward KL, Watkins H, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Meneton P, Magnusson PK, Nathan DM, Williams GH, Silander K, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Serrano-Ríos M, Lind L, Palmer LJ, Hu FB 1st, Franks PW, Ebrahim S, Marmot M, Kao WH, Pramstaller PP, Wright AF, Stumvoll M, Hamsten A, Buchanan TA, Valle TT, Rotter JI, Penninx BW, Boomsma DI, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Peltonen L, Mooser V, Sladek R, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Chasman DI, Johansen CT, Fouchier SW, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Feitosa MF, Orho-Melander M, Melander O, Li X, Li M, Cho YS, Go MJ, Kim YJ, Lee JY, Park T, Kim K, Sim X, Ong RT, Croteau-Chonka DC, Lange LA, Smith JD, Ziegler A, Zhang W, Zee RY, Whitfield JB, Thompson JR, Surakka I, Spector TD, Smit JH, Sinisalo J, Scott J, Saharinen J, Sabatti C, Rose LM, Roberts R, Rieder M, Parker AN, Pare G, O'Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, McArdle W, Masson D, Martin NG, Marroni F, Lucas G, Luben R, Lokki ML, Lettre G, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, König IR, Khaw KT, Kaplan LM, Johansson Å, Janssens AC, Igl W, Hovingh GK, Hengstenberg C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Groop LC, Gonzalez E, Freimer NB, Erdmann J, Ejebe KG, Döring A, Dominiczak AF, Demissie S, Deloukas P, de Faire U, Crawford G, Chen YD, Caulfield MJ, Boekholdt SM, Assimes TL, Quertermous T, Seielstad M, Wong TY, Tai ES, Feranil AB, Kuzawa CW, Taylor HA Jr, Gabriel SB, Holm H, Gudnason V, Krauss RM, Ordovas JM, Munroe PB, Kooner JS, Tall AR, Hegele RA, Kastelein JJ, Schadt EE, Strachan DP, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, and Kathiresan S
- Subjects
- Adiponectin genetics, Black or African American, Asian People, Cholesterol, HDL genetics, Female, Gene Expression, Genetic Predisposition to Disease, Glucose Tolerance Test, Humans, Insulin Resistance genetics, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, White People, Adiponectin blood, Diabetes Mellitus, Type 2 genetics, Genome-Wide Association Study
- Abstract
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance., Competing Interests: DM Waterworth, X Yuan, and VE Mooser are full-time employees of GlaxoSmithKline. P Vollenweider received grant money from GlaxoSmithKline to fund the CoLaus study. The other authors declare no competing financial interests.
- Published
- 2012
- Full Text
- View/download PDF
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