21 results on '"Roccasecca, Rosa Maria"'
Search Results
2. Dynamic protein interactions in the bacteriophage T4 replisome
- Author
-
Trakselis, Michael A., Mayer, M. Uljana, Ishmael, Faoud T., Roccasecca, Rosa Maria, and Benkovic, Stephen J.
- Subjects
Bacteriophages -- Research ,DNA ,Biological sciences ,Chemistry - Abstract
The bacteriophage T4 DNA replisome is a complex dynamic system employing a variety of proteins to orchestrate the synthesis of DNA on both the leading and lagging strands. Assembly of the protein complexes responsible for DNA synthesis and priming requires the coordination of transient biomolecular interactions. This interplay of proteins has been dissected through the use of small molecules including fluorescent probes and crosslinkers, enabling the development of a complex dynamic structural and kinetic model for DNA polymerase holoenzyme assembly and primosome formation.
- Published
- 2001
3. A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans
- Author
-
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
- Published
- 2012
4. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- Author
-
Willer, Cristen J, Scheet, Paul, Prokopenko, Inga, McCarroll, Steven A, Soranzo, Nicole, Weedon, Michael N, Lim, Noha, Speliotes, Elizabeth K, Bingham, Sheila A, Bergman, Richard N, Li, Shengxu, Heid, Iris M, Bennett, Amanda, Wheeler, Eleanor, Jackson, Anne U, Berndt, Sonja I, Sanna, Serena, Qi, Lu, Lindgren, Cecilia M, Papadakis, Konstantinos, Elliott, Amanda L, Tanaka, Toshiko, Zhao, Jing Hua, Almgren, Peter, Roccasecca, Rosa Maria, Lettre, Guillaume, Timpson, Nicholas J, Jacobs, Leonie C, Randall, Joshua C, Lamina, Claudia, Loos, Ruth J F, and Lyon, Helen N
- Abstract
Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10−8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
- Published
- 2009
- Full Text
- View/download PDF
5. Loss of FTO Antagonises Wnt Signaling and Leads to Developmental Defects Associated with Ciliopathies
- Author
-
Osborn, Daniel P. S., primary, Roccasecca, Rosa Maria, additional, McMurray, Fiona, additional, Hernandez-Hernandez, Victor, additional, Mukherjee, Sriparna, additional, Barroso, Inês, additional, Stemple, Derek, additional, Cox, Roger, additional, Beales, Philip L., additional, and Christou-Savina, Sonia, additional
- Published
- 2014
- Full Text
- View/download PDF
6. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
- Author
-
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.
- Published
- 2010
- Full Text
- View/download PDF
7. Erratum: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
- Author
-
Dupuis, Josée, primary, Langenberg, Claudia, additional, Prokopenko, Inga, additional, Saxena, Richa, additional, Soranzo, Nicole, additional, Jackson, Anne U, additional, Wheeler, Eleanor, additional, Glazer, Nicole L, additional, Bouatia-Naji, Nabila, additional, Gloyn, Anna L, additional, Lindgren, Cecilia M, additional, Mägi, Reedik, additional, Morris, Andrew P, additional, Randall, Joshua, additional, Johnson, Toby, additional, Elliott, Paul, additional, Rybin, Denis, additional, Thorleifsson, Gudmar, additional, Steinthorsdottir, Valgerdur, additional, Henneman, Peter, additional, Grallert, Harald, additional, Dehghan, Abbas, additional, Hottenga, Jouke Jan, additional, Franklin, Christopher S, additional, Navarro, Pau, additional, Song, Kijoung, additional, Goel, Anuj, additional, Perry, John R B, additional, Egan, Josephine M, additional, Lajunen, Taina, additional, Grarup, Niels, additional, Sparsø, Thomas, additional, Doney, Alex, additional, Voight, Benjamin F, additional, Stringham, Heather M, additional, Li, Man, additional, Kanoni, Stavroula, additional, Shrader, Peter, additional, Cavalcanti-Proença, Christine, additional, Kumari, Meena, additional, Qi, Lu, additional, Timpson, Nicholas J, additional, Gieger, Christian, additional, Zabena, Carina, additional, Rocheleau, Ghislain, additional, Ingelsson, Erik, additional, An, Ping, additional, O'Connell, Jeffrey, additional, Luan, Jian'an, additional, Elliott, Amanda, additional, McCarroll, Steven A, additional, Payne, Felicity, additional, Roccasecca, Rosa Maria, additional, Pattou, François, additional, Sethupathy, Praveen, additional, Ardlie, Kristin, additional, Ariyurek, Yavuz, additional, Balkau, Beverley, additional, Barter, Philip, additional, Beilby, John P, additional, Ben-Shlomo, Yoav, additional, Benediktsson, Rafn, additional, Bennett, Amanda J, additional, Bergmann, Sven, additional, Bochud, Murielle, additional, Boerwinkle, Eric, additional, Bonnefond, Amélie, additional, Bonnycastle, Lori L, additional, Borch-Johnsen, Knut, additional, Böttcher, Yvonne, additional, Brunner, Eric, additional, Bumpstead, Suzannah J, additional, Charpentier, Guillaume, additional, Chen, Yii-Der Ida, additional, Chines, Peter, additional, Clarke, Robert, additional, Coin, Lachlan J M, additional, Cooper, Matthew N, additional, Cornelis, Marilyn, additional, Crawford, Gabe, additional, Crisponi, Laura, additional, Day, Ian N M, additional, de Geus, Eco J C, additional, Delplanque, Jerome, additional, Dina, Christian, additional, Erdos, Michael R, additional, Fedson, Annette C, additional, Fischer-Rosinsky, Antje, additional, Forouhi, Nita G, additional, Fox, Caroline S, additional, Frants, Rune, additional, Franzosi, Maria Grazia, additional, Galan, Pilar, additional, Goodarzi, Mark O, additional, Graessler, Jürgen, additional, Groves, Christopher J, additional, Grundy, Scott, additional, Gwilliam, Rhian, additional, Gyllensten, Ulf, additional, Hadjadj, Samy, additional, Hallmans, Göran, additional, Hammond, Naomi, additional, Han, Xijing, additional, Hartikainen, Anna-Liisa, additional, Hassanali, Neelam, additional, Hayward, Caroline, additional, Heath, Simon C, additional, Hercberg, Serge, additional, Herder, Christian, additional, Hicks, Andrew A, additional, Hillman, David R, additional, Hingorani, Aroon D, additional, Hofman, Albert, additional, Hui, Jennie, additional, Hung, Joe, additional, Isomaa, Bo, additional, Johnson, Paul R V, additional, Jørgensen, Torben, additional, Jula, Antti, additional, Kaakinen, Marika, additional, Kaprio, Jaakko, additional, Kesaniemi, Y Antero, additional, Kivimaki, Mika, additional, Knight, Beatrice, additional, Koskinen, Seppo, additional, Kovacs, Peter, additional, Kyvik, Kirsten Ohm, additional, Lathrop, G Mark, additional, Lawlor, Debbie A, additional, Le Bacquer, Olivier, additional, Lecoeur, Cécile, additional, Li, Yun, additional, Lyssenko, Valeriya, additional, Mahley, Robert, additional, Mangino, Massimo, additional, Manning, Alisa K, additional, Martínez-Larrad, María Teresa, additional, McAteer, Jarred B, additional, McCulloch, Laura J, additional, McPherson, Ruth, additional, Meisinger, Christa, additional, Melzer, David, additional, Meyre, David, additional, Mitchell, Braxton D, additional, Morken, Mario A, additional, Mukherjee, Sutapa, additional, Naitza, Silvia, additional, Narisu, Narisu, additional, Neville, Matthew J, additional, Oostra, Ben A, additional, Orrù, Marco, additional, Pakyz, Ruth, additional, Palmer, Colin N A, additional, Paolisso, Giuseppe, additional, Pattaro, Cristian, additional, Pearson, Daniel, additional, Peden, John F, additional, Pedersen, Nancy L, additional, Perola, Markus, additional, Pfeiffer, Andreas F H, additional, Pichler, Irene, additional, Polasek, Ozren, additional, Posthuma, Danielle, additional, Potter, Simon C, additional, Pouta, Anneli, additional, Province, Michael A, additional, Psaty, Bruce M, additional, Rathmann, Wolfgang, additional, Rayner, Nigel W, additional, Rice, Kenneth, additional, Ripatti, Samuli, additional, Rivadeneira, Fernando, additional, Roden, Michael, additional, Rolandsson, Olov, additional, Sandbaek, Annelli, additional, Sandhu, Manjinder, additional, Sanna, Serena, additional, Sayer, Avan Aihie, additional, Scheet, Paul, additional, Scott, Laura J, additional, Seedorf, Udo, additional, Sharp, Stephen J, additional, Shields, Beverley, additional, SigurÐsson, Gunnar, additional, Sijbrands, Eric J G, additional, Silveira, Angela, additional, Simpson, Laila, additional, Singleton, Andrew, additional, Smith, Nicholas L, additional, Sovio, Ulla, additional, Swift, Amy, additional, Syddall, Holly, additional, Syvänen, Ann-Christine, additional, Tanaka, Toshiko, additional, Thorand, Barbara, additional, Tichet, Jean, additional, Tönjes, Anke, additional, Tuomi, Tiinamaija, additional, Uitterlinden, André G, additional, van Dijk, Ko Willems, additional, van Hoek, Mandy, additional, Varma, Dhiraj, additional, Visvikis-Siest, Sophie, additional, Vitart, Veronique, additional, Vogelzangs, Nicole, additional, Waeber, Gérard, additional, Wagner, Peter J, additional, Walley, Andrew, additional, Walters, G Bragi, additional, Ward, Kim L, additional, Watkins, Hugh, additional, Weedon, Michael N, additional, Wild, Sarah H, additional, Willemsen, Gonneke, additional, Witteman, Jaqueline C M, additional, Yarnell, John W G, additional, Zeggini, Eleftheria, additional, Zelenika, Diana, additional, Zethelius, Björn, additional, Zhai, Guangju, additional, Zhao, Jing Hua, additional, Zillikens, M Carola, additional, Consortium, DIAGRAM, additional, Consortium, GIANT, additional, Consortium, Global BPgen, additional, Borecki, Ingrid B, additional, Loos, Ruth J F, additional, Meneton, Pierre, additional, Magnusson, Patrik K E, additional, Nathan, David M, additional, Williams, Gordon H, additional, Hattersley, Andrew T, additional, Silander, Kaisa, additional, Salomaa, Veikko, additional, Smith, George Davey, additional, Bornstein, Stefan R, additional, Schwarz, Peter, additional, Spranger, Joachim, additional, Karpe, Fredrik, additional, Shuldiner, Alan R, additional, Cooper, Cyrus, additional, Dedoussis, George V, additional, Serrano-Ríos, Manuel, additional, Morris, Andrew D, additional, Lind, Lars, additional, Palmer, Lyle J, additional, Hu, Frank B, additional, Franks, Paul W, additional, Ebrahim, Shah, additional, Marmot, Michael, additional, Kao, W H Linda, additional, Pankow, James S, additional, Sampson, Michael J, additional, Kuusisto, Johanna, additional, Laakso, Markku, additional, Hansen, Torben, additional, Pedersen, Oluf, additional, Pramstaller, Peter Paul, additional, Wichmann, H Erich, additional, Illig, Thomas, additional, Rudan, Igor, additional, Wright, Alan F, additional, Stumvoll, Michael, additional, Campbell, Harry, additional, Wilson, James F, additional, Hamsten, Anders, additional, Bergman, Richard N, additional, Buchanan, Thomas A, additional, Collins, Francis S, additional, Mohlke, Karen L, additional, Tuomilehto, Jaakko, additional, Valle, Timo T, additional, Altshuler, David, additional, Rotter, Jerome I, additional, Siscovick, David S, additional, Penninx, Brenda W J H, additional, Boomsma, Dorret I, additional, Deloukas, Panos, additional, Spector, Timothy D, additional, Frayling, Timothy M, additional, Ferrucci, Luigi, additional, Kong, Augustine, additional, Thorsteinsdottir, Unnur, additional, Stefansson, Kari, additional, van Duijn, Cornelia M, additional, Aulchenko, Yurii S, additional, Cao, Antonio, additional, Scuteri, Angelo, additional, Schlessinger, David, additional, Uda, Manuela, additional, Ruokonen, Aimo, additional, Jarvelin, Marjo-Riitta, additional, Waterworth, Dawn M, additional, Vollenweider, Peter, additional, Peltonen, Leena, additional, Mooser, Vincent, additional, Abecasis, Goncalo R, additional, Wareham, Nicholas J, additional, Sladek, Robert, additional, Froguel, Philippe, additional, Watanabe, Richard M, additional, Meigs, James B, additional, Groop, Leif, additional, Boehnke, Michael, additional, McCarthy, Mark I, additional, Florez, Jose C, additional, and Barroso, Inês, additional
- Published
- 2010
- Full Text
- View/download PDF
8. Characterization and expression analysis of the Spink5 gene, the mouse ortholog of the defective gene in Netherton syndrome
- Author
-
Galliano, Marie Florence, primary, Roccasecca, Rosa Maria, additional, Descargues, Pascal, additional, Micheloni, Alessia, additional, Levy, Elaine, additional, Zambruno, Giovanna, additional, D'Alessio, Marina, additional, and Hovnanian, Alain, additional
- Published
- 2005
- Full Text
- View/download PDF
9. Dissociative Properties of the Proteins within the Bacteriophage T4 Replisome
- Author
-
Trakselis, Michael A., primary, Roccasecca, Rosa Maria, additional, Yang, Jingsong, additional, Valentine, Ann M., additional, and Benkovic, Stephen J., additional
- Published
- 2003
- Full Text
- View/download PDF
10. The Application of a Minicircle Substrate in the Study of the Coordinated T4 DNA Replication
- Author
-
Yang, Jingsong, primary, Trakselis, Michael A., additional, Roccasecca, Rosa Maria, additional, and Benkovic, Stephen J., additional
- Published
- 2003
- Full Text
- View/download PDF
11. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus
- Author
-
Scarselli, Elisa, primary, Ansuini, Helenia, additional, Cerino, Raffaele, additional, Roccasecca, Rosa Maria, additional, Acali, Stefano, additional, Filocamo, Gessica, additional, Traboni, Cinzia, additional, Nicosia, Alfredo, additional, Cortese, Riccardo, additional, and Vitelli, Alessandra, additional
- Published
- 2002
- Full Text
- View/download PDF
12. A model for the hepatitis C virus envelope glycoprotein E2
- Author
-
Yagnik, Asutosh T., primary, Lahm, Armin, additional, Meola, Annalisa, additional, Roccasecca, Rosa Maria, additional, Ercole, Bruno B., additional, Nicosia, Alfredo, additional, and Tramontano, Anna, additional
- Published
- 2000
- Full Text
- View/download PDF
13. Loss of FTO Antagonises Wnt Signaling and Leads to Developmental Defects Associated with Ciliopathies.
- Author
-
Osborn, Daniel P. S., Roccasecca, Rosa Maria, McMurray, Fiona, Hernandez-Hernandez, Victor, Mukherjee, Sriparna, Barroso, Inês, Stemple, Derek, Cox, Roger, Beales, Philip L., and Christou-Savina, Sonia
- Subjects
- *
OBESITY risk factors , *OBESITY genetics , *WNT genes , *CELLULAR signal transduction , *DEVELOPMENTAL biology , *DEVELOPMENTAL disabilities , *CELL migration , *CHROMOSOMAL translocation - Abstract
Common intronic variants in the Human fat mass and obesity-associated gene (FTO) are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish) and in vitro (Fto−/− MEFs and HEK293T). Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca2+ pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
14. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.
- Author
-
Willer, Cristen J., Speliotes, Elizabeth K., Loos, Ruth J. F., Shengxu Li, Lindgren, Cecilia M., Heid, Iris M., Berndt, Sonja I., Elliott, Amanda L., Jackson, Anne U., Lamina, Claudia, Lettre, Guillaume, Lim, Noha, Lyon, Helen N., McCarroll, Steven A., Papadakis, Konstantinos, Lu Qi, Randall, Joshua C., Roccasecca, Rosa Maria, Sanna, Serena, and Scheet, Paul
- Subjects
GENOMES ,BODY mass index ,META-analysis ,COHORT analysis ,OBESITY ,GENETIC polymorphisms ,MONOGENIC functions ,CENTRAL nervous system - Abstract
Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10
−8 ): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
15. Binding of the Hepatitis C Virus E3 Glycoprotein to CD81 Is Strain Specific and Is Modulated by a Complex Interplay between Hypervariable Regions 1 and 2.
- Author
-
Roccasecca, Rosa Maria, Ansuini, Helenia, Vitelli, Alessandra, Meola, Annalisa, Scarselli, Elisa, Acali, Stefano, Pezzanera, Monica, Ercole, Bruno Bruni, McKeating, Jane, Yagnik, Asutosh, Lahm, Armin, Tramontano, Anna, Cortese, Riccardo, and Nicosia, Alfredo
- Subjects
- *
GLYCOPROTEINS , *HYPERVARIABLE regions , *HEPATITIS C virus - Abstract
The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies and is presently being evaluated as an HCV vaccine candidate. HCV binds to human cells through the interaction of E2 with the tetraspanin CD81, a putative viral receptor component. We have analyzed four different E2 proteins from la and lb viral isolates for their ability to bind to recombinant CD81 in vitro and to the native receptor displayed on the surface of Molt-4 cells. A substantial difference in binding efficiency between these E2 variants was observed, with proteins derived from lb subtypes showing significantly lower binding than the la protein. To elucidate the mechanism of E2-CD81 interaction and to identify critical regions responsible for the different binding efficiencies of the E2 variants, several mutants were generated in E2 protein regions predicted by computer modeling to be exposed on the protein surface. Functional analysis of these E2 derivatives revealed that at least two distinct domains are responsible for interaction with CD81. A first segment centered around amino acid residues 613 to 618 is essential for recognition, while a second element including the two hypervariable regions (HVRs) modulates E2 receptor binding. Binding inhibition experiments with anti-HVR monoclonal antibodies confirmed this mapping and supported the hypothesis that a complex interplay between the two HVRs of E2 is responsible for modulating receptor binding, possibly through intramolecular interactions. Finally, E2 proteins from different isolates displayed a profile of binding to human hepatic cells different from that observed on Molt-4 cells or isolated recombinant CD81, indicating that additional factors are involved in viral recognition by target liver cells. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
16. 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
-
Dastani, Zari, Hivert, Marie-France, Timpson, Nicholas, Perry, John RB, Yuan, Xin, Scott, Robert A, Henneman, Peter, Heid, Iris M, Kizer, Jorge R, Lyytikäinen, Leo-Pekka, Fuchsberger, Christian, Tanaka, Toshiko, Morris, Andrew P, Small, Kerrin, Isaacs, Aaron, Beekman, Marian, Coassin, Stefan, Lohman, Kurt, Qi, Lu, Kanoni, Stavroula, Pankow, James S, Uh, Hae-Won, Wu, Ying, Bidulescu, Aurelian, Rasmussen-Torvik, Laura J, Greenwood, Celia MT, Ladouceur, Martin, Grimsby, Jonna, Manning, Alisa K, Liu, Ching-Ti, Kooner, Jaspal, Mooser, Vincent E, Vollenweider, Peter, Kapur, Karen A, Chambers, John, Wareham, Nicholas J, Langenberg, Claudia, Frants, Rune, Willems-Vandijk, Ko, Oostra, Ben A, Willems, Sara M, Lamina, Claudia, Winkler, Thomas W, Psaty, Bruce M, Tracy, Russell P, Brody, Jennifer, Chen, Ida, Viikari, Jorma, Kähönen, Mika, Pramstaller, Peter P, Evans, David M, St Pourcain, Beate, Sattar, Naveed, Wood, Andrew R, Bandinelli, Stefania, Carlson, Olga D, Egan, Josephine M, Böhringer, Stefan, Van Heemst, Diana, Kedenko, Lyudmyla, Kristiansson, Kati, Nuotio, Marja-Liisa, Loo, Britt-Marie, Harris, Tamara, Garcia, Melissa, Kanaya, Alka, Haun, Margot, Klopp, Norman, Wichmann, H-Erich, Deloukas, Panos, Katsareli, Efi, Couper, David J, Duncan, Bruce B, Kloppenburg, Margreet, Adair, Linda S, Borja, Judith B, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, Wilson, James G, Musani, Solomon, Guo, Xiuqing, Johnson, Toby, Semple, Robert, Teslovich, Tanya M, Allison, Matthew A, Redline, Susan, Buxbaum, Sarah G, Mohlke, Karen L, Meulenbelt, Ingrid, Ballantyne, Christie M, Dedoussis, George V, Hu, Frank B, Liu, Yongmei, Paulweber, Bernhard, Spector, Timothy D, Slagboom, P Eline, Ferrucci, Luigi, Jula, Antti, Perola, Markus, Raitakari, Olli, Florez, Jose C, Salomaa, Veikko, Eriksson, Johan G, Frayling, Timothy M, Hicks, Andrew A, Lehtimäki, Terho, Smith, George Davey, Siscovick, David S, Kronenberg, Florian, Van Duijn, Cornelia, Loos, Ruth JF, Waterworth, Dawn M, Meigs, James B, Dupuis, Josee, Richards, J Brent, Voight, Benjamin F, Scott, Laura J, Steinthorsdottir, Valgerdur, 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, Hofmann, Oliver M, 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, 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, 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, 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, Morris, Andrew D, Palmer, Colin NA, Rudan, Igor, Sijbrands, Eric, Stein, Lincoln D, Tuomilehto, Jaakko, Uitterlinden, Andre, Walker, Mark, Watanabe, Richard M, Abecasis, Goncalo R, Boehm, Bernhard O, Campbell, Harry, Daly, Mark J, Hattersley, Andrew T, Pedersen, Oluf, Barroso, Inês, 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, Elliott, Paul, Rybin, Denis, Dehghan, Abbas, Hottenga, Jouke Jan, Song, Kijoung, Goel, Anuj, Lajunen, Taina, Doney, Alex, 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, 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, Hillman, David R, Hingorani, Aroon D, Hui, Jennie, Hung, Joe, 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, 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, Orrù, Marco, Pakyz, Ruth, Paolisso, Giuseppe, Pattaro, Cristian, Pearson, Daniel, Peden, John F, Pedersen, Nancy L, Pfeiffer, Andreas FH, Pichler, Irene, Polasek, Ozren, Posthuma, Danielle, Potter, Simon C, Pouta, Anneli, Province, Michael A, 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, Sigurðsson, Gunnar, Sijbrands, Eric JG, Silveira, Angela, Simpson, Laila, Singleton, Andrew, Smith, Nicholas L, Sovio, Ulla, Swift, Amy, Syddall, Holly, Syvänen, Ann-Christine, 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, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Borecki, Ingrid B, Meneton, Pierre, Magnusson, Patrik KE, Nathan, David M, Williams, Gordon H, Silander, Kaisa, Bornstein, Stefan R, Schwarz, Peter, Spranger, Joachim, Karpe, Fredrik, Shuldiner, Alan R, Cooper, Cyrus, 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, Procardis Consortium, Buchanan, Thomas A, Valle, Timo T, Rotter, Jerome I, Penninx, Brenda WJH, Boomsma, Dorret I, Cao, Antonio, Scuteri, Angelo, Schlessinger, David, Uda, Manuela, Ruokonen, Aimo, Jarvelin, Marjo-Riitta, Peltonen, Leena, Mooser, Vincent, Sladek, Robert, MAGIC Investigators, GLGC Consortium, Musunuru, Kiran, Smith, Albert V, Edmondson, Andrew C, Stylianou, Ioannis M, Koseki, Masahiro, Pirruccello, James P, Chasman, Daniel I, Johansen, Christopher T, Fouchier, Sigrid W, Peloso, Gina M, Barbalic, Maja, Ricketts, Sally L, Bis, Joshua C, Feitosa, Mary F, Orho-Melander, Marju, Melander, Olle, Li, Xiaohui, Li, Mingyao, Cho, Yoon Shin, Go, Min Jin, Kim, Young Jin, Lee, Jong-Young, Park, Taesung, Kim, Kyunga, Sim, Xueling, Ong, Rick Twee-Hee, Croteau-Chonka, Damien C, Lange, Leslie A, Smith, Joshua D, Ziegler, Andreas, Zhang, Weihua, Zee, Robert YL, Whitfield, John B, Thompson, John R, Surakka, Ida, Spector, Tim D, Smit, Johannes H, Sinisalo, Juha, Scott, James, Saharinen, Juha, Sabatti, Chiara, Rose, Lynda M, Roberts, Robert, Rieder, Mark, Parker, Alex N, Pare, Guillaume, O'Donnell, Christopher J, Nieminen, Markku S, Nickerson, Deborah A, Montgomery, Grant W, McArdle, Wendy, Masson, David, Martin, Nicholas G, Marroni, Fabio, Lucas, Gavin, Luben, Robert, Lokki, Marja-Liisa, Lettre, Guillaume, Launer, Lenore J, Lakatta, Edward G, Laaksonen, Reijo, Kyvik, Kirsten O, König, Inke R, Khaw, Kay-Tee, Kaplan, Lee M, Johansson, Åsa, Janssens, A Cecile JW, Igl, Wilmar, Hovingh, G Kees, Hengstenberg, Christian, Havulinna, Aki S, Hastie, Nicholas D, Harris, Tamara B, Haritunians, Talin, Hall, Alistair S, Groop, Leif C, Gonzalez, Elena, Freimer, Nelson B, Erdmann, Jeanette, Ejebe, Kenechi G, Döring, Angela, Dominiczak, Anna F, Demissie, Serkalem, Deloukas, Panagiotis, De Faire, Ulf, Crawford, Gabriel, Chen, Yii-Der I, Caulfield, Mark J, Boekholdt, S Matthijs, Assimes, Themistocles L, Quertermous, Thomas, Seielstad, Mark, Wong, Tien Y, Tai, E-Shyong, Feranil, Alan B, Kuzawa, Christopher W, Taylor, Herman A, Gabriel, Stacey B, Holm, Hilma, Gudnason, Vilmundur, Krauss, Ronald M, Ordovas, Jose M, Munroe, Patricia B, Kooner, Jaspal S, Tall, Alan R, Hegele, Robert A, Kastelein, John JP, Schadt, Eric E, Strachan, David P, Reilly, Muredach P, Samani, Nilesh J, Schunkert, Heribert, Cupples, L Adrienne, Sandhu, Manjinder S, Ridker, Paul M, Rader, Daniel J, and Kathiresan, Sekar
- Subjects
2. Zero hunger ,Male ,Waist-Hip Ratio ,Cholesterol, HDL ,Gene Expression ,Glucose Tolerance Test ,Polymorphism, Single Nucleotide ,White People ,3. Good health ,Black or African American ,Asian People ,Diabetes Mellitus, Type 2 ,Humans ,Female ,Genetic Predisposition to Disease ,Adiponectin ,Insulin Resistance ,Metabolic Networks and Pathways ,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
17. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
- Author
-
Global BPgen Consrotium, Sovio, Ulla, Shuldiner, Alan R., Dedoussis, George V., Bonnycastle, Lori L., Hercberg, Serge, Chen, Yii-Der Ida, Visvikis-Siest, Sophie, Kumari, Meena, Meneton, Pierre, Ariyurek, Yavuz, Egan, Josephine M., Ben-Shlomo, Yoav, Forouhi, Nita G., Graessler, Jurgen, Rudan, Igor, Pedersen, Nancy L., Lindgren, Cecilia M., Chines, Peter, Stringham, Heather M., Meisinger, Christa, Pattaro, Cristian, Vogelzangs, Nicole, DIAGRAM Consortium, Illig, Thomas, Langenberg, Claudia, Zethelius, Bjorn, Sayer, Avan Aihie, Laakso, Markku, Li, Man, Clarke, Robert, Isomaa, Bo, McAteer, Jarred B., Doney, Alex, Pedersen, Oluf, Jorgensen, Torben, Bottcher, Yvonne, Ebrahim, Shah, Schwarz, Peter, Lecoeur, Cecile, Psaty, Bruce M., Shrader, Peter, Knight, Beatrice, Beilby, John P., Gieger, Christian, Ripatti, Samuli, Zhao, Jing Hua, Herder, Christian, Morken, Mario A., Kesaniemi, Y. Antero, Orru, Marco, Mitchell, Braxton D., Thorand, Barbara, Lyssenko, Valeriya, Manning, Alisa K., Sethupathy, Praveen, Meyre, David, Hansen, Torben, Rayner, Nigel W., Hammond, Naomi, Timpson, Nicholas J., Sanna, Serena, Brunner, Eric, Zhai, Guangju, Witteman, Jacqueline C.M., Rybin, Denis, Cornelis, Marilyn, Zabena, Carina, Willemson, Gonneke, Kaakinen, Marika, Perry, John R.B., Zelenika, Diana, Walters, G. Bragi, Heath, Simon C., Oostra, Ben A., Salomaa, Veikko, Ward, Kim L., van Dijk, Ko Willems, Williams, Gordon H., Karpe, Fredrik, Wagner, Peter J., Magi, Reedik, Fischer-Rosinsky, Antje, Hallmans, Goran, Lajunen, Taina, Qi, Lu, Navarro, Paul, Grallert, Harald, Pramstaller, Peter Paul, Kaprio, Jaakko, Smith, Nicholas L., Hayward, Caroline, Sandbaek, Annelli, Sparso, Thomas, Dina, Christian, Paolisso, Giuseppe, Wright, Alan F., Mangino, Massimo, Henneman, Peter, Smith, George Davey, Boerwinkle, Eric, Prokopenko, Inga, Jackson, Anne U., Grarup, Niels, Walley, Andrew, Hofman, Albert, Hadjadj, Samy, Hu, Frank B., Hung, Joe, Li, Yun, Gwilliam, Rhian, Thorleifsson, Gudmar, Singleton, Andrew, Ardlie, Kristin, Kivimaki, Mika, Syvanen, Ann-Christine, Zillikens, M. Carola, Day, Ian N.M., Rice, Kenneth, Silander, Kaisa, Bergmann, Sven, Simpson, Laila, Scott, Laura J., Melzer, David, Neville, Matthew J., Watkins, Hugh, Ingelsson, Erik, Lathrop, G. Mark, Scheet, Paul, Hottenga, Jouke Jan, Song, Kijoung, Benediktsson, Rafn, de Geus, Eco J. C., Le Bacquer, Olivier, Hillman, David R., Koskinen, Seppo, Frants, Rune, Lind, Lars, Kanoni, Stavroula, Sandhu, Manjinder, Crawford, Gabe, Sigurdsson, Gunnar, Pfeiffer, Andreas F.H., Pattou, Francois, Pankow, James S., Wilson, James F., Bennett, Amanda J., Dupuis, Josee, Potter, Simon C., Elliott, Amanda, Province, Michael A., Perola, Markus, Serrano-Rios, Manuel, Kyvik, Kirsten Ohm, Yarnell, John W.G., Pakyz, Ruth, Johnson, Paul R.V., Borch-Johnsen, Knut, Saxena, Richa, Steinthorsdottir, Valgerdur, Tanaka, Toshiko, Campbell, Harry, Barter, Philip, Franzosi, Maria Grazia, GIANT Consortium, Han, Xijing, Cavalcanti-Proenca, Christine, Glazer, Nicole L., Kovacs, Peter, Stumvoll, Michael, Syddall, Holly, Hingorani, Aroon D., Morris, Andrew P., O'Connell, Jeffrey, Payne, Felicity, Galan, Pilar, Rivadeneira, Fernando, Wild, Sarah H., McPherson, Ruth, Sijbrands, Eric J.G., Hicks, Andrew A., Dehghan, Abbas, Elliott, Paul, Cooper, Matthew N., Sharp, Stephen J., Balkau, Beverley, Voight, Benjamin F., Roden, Michael, Tuomi, Tiinamaija, Franklin, Christopher S., Swift, Amy, Pichler, Irene, Narisu, Narisu, Goodarzi, Mark O., Franks, Paul W., An, Ping, Bumpstead, Suzannah J., Bochud, Murielle, Rathmann, Wolfgang, Randall, Joshua, Bouatia-Naji, Nabila, von Hoek, Mandy, Kuusisto, Johanna, Sampson, Michael J., Wichmann, H. Erich, Vitart, Veronique, Tichet, Jean, Spranger, Joachim, Fedson, Annette C., Waeber, Gerard, Wheeler, Eleanor, Polasek, Ozren, Coin, Lachlan J.M., Varma, Dhiraj, Pearson, Daniel, Hartikainen, Anna-Liisa, Loos, Ruth J.F., Grundy, Scott, Martinez-Larrad, Maria Teresa, Jula, Antti, Palmer, Colin N.A., Mukherjee, Sutapa, Bornstein, Stefan R., Gyllensten, Ulf, Roccasecca, Rosa Maria, Johnson, Toby, Crisponi, Laura, Weedon, Michael N., Hamsten, Anders, Bonnefond, Amelie, Nathan, David M., Silveira, Angela, Borecki, Ingrid B., Hassanali, Neelam, Pouta, Anneli, Fox, Caroline S., Cooper, Cyrus, McCulloch, Laura J., Hattersley, Andrew T., Seedorf, Udo, Zeggini, Eleftheria, Lawlor, Debbie A., Uitterlinden, Andre G., Rocheleau, Ghislain, Kao, W.H. Linda, Goel, Anuj, Palmer, Lyel J., Magnusson, Patrik K.E., Shields, Beverley, Tonjes, Anke, Soranzo, Nicole, Groves, Christopher J., Gloyn, Anna L., Charpentier, Guillaume, Erdos, Michael R., Posthuma, Danielle, Marmot, Michael, Morris, Andrew D., Luan, Jian'an, Delplanque, Jerome, Naitza, Silvia, Mahley, Robert, McCarroll, Steven A., Hui, Jennie, Rolandsson, Olov, and Peden, John F.
- Subjects
3. Good health - 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.
18. The Application of a Minicircle Substrate in the Study of the Coordinated T4 DNA Replication.
- Author
-
Jingsong Yang, Trakselis, Michael A., Roccasecca, Rosa Maria, and Benkovic, Stephen J.
- Subjects
- *
DNA replication , *BACTERIOPHAGES , *NUCLEOTIDES - Abstract
A reconstituted in vitro bacteriophage T4 DNA replication system was studied on a synthetic 70-met minicircle substrate. This substrate was designed so that dGMP and dCMP were exclusively incorporated into the leading and the lagging strand, respectively. This design allows the simultaneous and independent measurement of the leading and lagging strand synthesis. In this paper, we report our results on the characterization of the 70-mer minicircle substrate. We show here that the minicircle substrate supports coordinated leading and lagging strand synthesis under the experimental conditions employed. The rate of the leading strand fork movement was at an average of ∼150 nucleotides/s. This rate decreased to less than 30 nucleotides/s when the helicase was omitted from the reaction. These results suggest that both the holoenzyme and the primosome can be simultaneously assembled onto the minicircle substrate. The lagging strand synthesized on this substrate is of an average of 1.5 kb, and the length of the Okazaki fragments increased with decreasing [rNTPs]. The proper response of the Okazaki fragment size toward the change of the priming signal further indicates a functional replisome assembled on the minicircle template. The effects of various protein components on the leading and lagging strand synthesis were also studied. The collective results indicate that coordinated strand synthesis only takes place within certain protein concentration ranges. The optimal protein levels of the proteins that constitute the T4 replisome generally bracket the concentrations of the same proteins in vivo. Omission of the primase has little effect on the rate of dNMP incorporation or the rate of the fork movement on the leading strand within the first 30 s of the reaction. This inhibition only becomes significant at later times of the reaction and may be associated with the accumulation of single-stranded DNA leading to the collapse of active replisomes. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
19. A genome-wide association search for type 2 diabetes genes in African Americans.
- Author
-
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
20. 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
-
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
21. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
- Author
-
Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, Wheeler E, Glazer NL, Bouatia-Naji N, Gloyn AL, Lindgren CM, Mägi R, Morris AP, Randall J, Johnson T, Elliott P, Rybin D, Thorleifsson G, Steinthorsdottir V, Henneman P, Grallert H, Dehghan A, Hottenga JJ, Franklin CS, Navarro P, Song K, Goel A, Perry JR, Egan JM, Lajunen T, Grarup N, Sparsø T, Doney A, Voight BF, Stringham HM, Li M, Kanoni S, Shrader P, Cavalcanti-Proença C, Kumari M, Qi L, Timpson NJ, Gieger C, Zabena C, Rocheleau G, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, McCarroll SA, Payne F, Roccasecca RM, Pattou F, Sethupathy P, Ardlie K, Ariyurek Y, Balkau B, Barter P, Beilby JP, Ben-Shlomo Y, Benediktsson R, Bennett AJ, Bergmann S, Bochud M, Boerwinkle E, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Charpentier G, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Cornelis M, Crawford G, Crisponi L, Day IN, de Geus EJ, Delplanque J, Dina C, Erdos MR, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Fox CS, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Groves CJ, Grundy S, Gwilliam R, Gyllensten U, Hadjadj S, Hallmans G, Hammond N, Han X, Hartikainen AL, Hassanali N, Hayward C, Heath SC, Hercberg S, Herder C, Hicks AA, Hillman DR, Hingorani AD, Hofman A, Hui J, Hung J, Isomaa B, Johnson PR, Jørgensen T, 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, Lyssenko V, Mahley R, Mangino M, Manning AK, Martínez-Larrad MT, McAteer JB, McCulloch LJ, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Morken MA, Mukherjee S, Naitza S, Narisu N, Neville MJ, Oostra BA, Orrù M, Pakyz R, Palmer CN, 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, Rathmann W, Rayner NW, Rice K, Ripatti S, Rivadeneira F, Roden M, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Scott LJ, Seedorf U, Sharp SJ, Shields B, Sigurethsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Thorand B, Tichet J, Tönjes A, Tuomi T, Uitterlinden AG, van Dijk KW, van Hoek M, Varma D, Visvikis-Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Walters GB, Ward KL, Watkins H, Weedon MN, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zeggini E, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Hattersley AT, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano-Ríos M, Morris AD, Lind L, Palmer LJ, Hu FB, Franks PW, Ebrahim S, Marmot M, Kao WH, Pankow JS, Sampson MJ, Kuusisto J, Laakso M, Hansen T, Pedersen O, Pramstaller PP, Wichmann HE, Illig T, Rudan I, Wright AF, Stumvoll M, Campbell H, Wilson JF, Bergman RN, Buchanan TA, Collins FS, Mohlke KL, Tuomilehto J, Valle TT, Altshuler D, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Frayling TM, Ferrucci L, Kong A, Thorsteinsdottir U, Stefansson K, van Duijn CM, Aulchenko YS, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Abecasis GR, Wareham NJ, Sladek R, Froguel P, Watanabe RM, Meigs JB, Groop L, Boehnke M, McCarthy MI, Florez JC, and Barroso I
- Subjects
- Adolescent, Adult, Alleles, Child, DNA Copy Number Variations genetics, Databases, Genetic, Delta-5 Fatty Acid Desaturase, Gene Expression Regulation, Genome-Wide Association Study, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci genetics, Quantitative Trait, Heritable, Reproducibility of Results, Blood Glucose genetics, Blood Glucose metabolism, Diabetes Mellitus, Type 2 genetics, Fasting blood, Genetic Loci genetics, Genetic Predisposition to Disease, Homeostasis genetics
- 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.
- Published
- 2010
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.