المؤلفون: Acosta-Herrera, Marialbert, Kerick, Martin, González-Serna, David, Wijmenga, Cisca, Franke, Andre, Gregersen, Peter K., Padyukov, Leonid, Worthington, J., Vyse, T. J., Alarcón-Riquelme, M. E., Mayes, M. D., Martín, J., Miller, Frederick W., Chen, Wei, O'Hanlon, Terrance P., Cooper, Robert G., Vencovsky, Jiri, Rider, Lisa G, Danko, Katalin, Wedderburn, Lucy R., Lundberg, Ingrid E., Pachman, Lauren M., Reed, Ann M., Ytterberg, Steven R, Selva-O'Callaghan, Alber, Radstake, Timothy R., Isenberg, David A, Chinoy, Hector, Ollier, William E. R, Scheet, Paul, Peng, Bo, Lee, Annette, Lamb, Janine A., Amos, Christopher I., Denton, Christopher, Hilton-Jones, David, Plotz, Paul H., Varsani, Hemlata, Radstake, Timothy R. D. J., Gorlova, Olga, Rueda, B., Martín, J. E., Alizadeh, B. Z., Palomino-Morales, Rogelio, Coenen, Marieke J. H., Vonk, Madelon C., Voskuyl, Alexandre E., Scheurwegh, Annemie J., Broen, Jasper C., van Riel, Piet L. C. M., van 't Slot, Rubén, Italiaander, Annet, Ophoff, Roel A., Riemekasten, Gabriela, Hunzelmann, Nicolas, Simeon, Carmen P., Ortego-Centeno, N., González-Gay, M. A., González-Escribano, María Francisca, Airó, Paolo, van Laar, Jaap, Herrick, Ariane L., Hesselstrand, Roger, Smith, Vanessa, de Keyser, Filip, Houssiau, Fredric, Chee, Meng May, Madhok, Rajan, Shiels, Paul, Westhovens, Rene, Kreuter, A., Kiener, Hans, de Baere, Elfride, Witte, Torsten, Klareskog, Lars, Beretta, Lorenzo, Scorza, Rafaella, Lie, Benedicte A., Hoffman-Vold, A. M., Carreira, P., Varga, John, Hinchcliff, Monique, Lee, Annette T., Ying, Jun, Han, Younghun, Weng, Shih-Feng, Wigley, Fredrick M., Hummers, L. K., Nelson, J. Lee, Agarwal, Sandeep K., Assassi, S., Gourh, Pravitt, Tan, Filemon K., Koeleman, B. P., Arnett, Frank C., Myositis Genetics Consortium, Scleroderma Genetics Consortium.

المساهمون: Innovative Medicines Initiative, Ministerio de Economía, Industria y Competitividad (España), Junta de Andalucía, National Institute of Environmental Health Sciences (US), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Polymer Chemistry and Bioengineering, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Myositis Genetics Consortium, Scleroderma Genetics Consortium

المصدر: Digital.CSIC. Repositorio Institucional del CSIC
instname
Acosta-Herrera, M, Kerick, M, Gonzalez-Serna, D, Wijmenga, C, Franke, A, Gregersen, P K, Padyukov, L, Worthington, J, Vyse, T, Alarcón-Riquelme, M E, Mayes, M D & Martin, J 2019, ' Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases ', Annals Of Rheumatic Diseases, vol. 78, pp. 311-319 . https://doi.org/10.1136/annrheumdis-2018-214127Test
Annals of the rheumatic diseases, vol 78, iss 3
Annals of the Rheumatic Diseases, 78, 3, pp. 311-319
Annals of the Rheumatic Diseases, 78, 311-319
Annals of the Rheumatic Diseases, 78(3), 311-319. BMJ PUBLISHING GROUP
Annals of the rheumatic diseases

مصطلحات موضوعية: 0301 basic medicine, Male, Lydia Becker Institute, PATHOGENESIS, PROTEIN, Arthritis, VARIANTS, medicine.disease_cause, Myositis Genetics Consortium, Autoimmunity, Scleroderma, Arthritis, Rheumatoid, 0302 clinical medicine, Scleroderma Genetics Consortium, Rheumatoid, MULTIPLE, Lupus Erythematosus, Systemic, Immunology and Allergy, Medicine, 2.1 Biological and endogenous factors, Aetiology, Genetics, autoimmunity, Family aggregation, Lim Kinases, ASSOCIATION, Single Nucleotide, Public Health and Health Services, Female, ARTHRITIS, Life Sciences & Biomedicine, alpha Karyopherins, Adult, medicine.medical_specialty, GENETICS, gene polymorphism, Quantitative Trait Loci, Clinical Sciences, Immunology, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Autoimmune Disease, General Biochemistry, Genetics and Molecular Biology, White People, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, Immune system, Rheumatology, Internal medicine, Rheumatic Diseases, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, Humans, Genetic Predisposition to Disease, autoimmune diseases, Polymorphism, SCLEROSIS, COMMON, 030203 arthritis & rheumatology, Science & Technology, Scleroderma, Systemic, COMPLEX, Myositis, Lupus Erythematosus, business.industry, Inflammatory and immune system, Systemic, Human Genome, Membrane Proteins, medicine.disease, Arthritis & Rheumatology, Repressor Proteins, 030104 developmental biology, Expression quantitative trait loci, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Human medicine, Gene polymorphism, business, Genome-Wide Association Study

الوصف: ObjectiveImmune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.

وصف الملف: application/pdf; Print-Electronic

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::840aa90000136e8bcda9414e9db777dbTest
http://hdl.handle.net/10261/200275Test

المؤلفون: Franić, Sanja, Groen-Blokhuis, Maria M, Dolan, Conor V, Kattenberg, Mathijs V, Pool, René, Xiao, Xiangjun, Scheet, Paul A, Ehli, Erik A, Davies, Gareth E, van der Sluis, Sophie, Abdellaoui, Abdel, Hansell, Narelle K, Martin, Nicholas G, Hudziak, James J, van Beijsterveldt, Catherina E M, Swagerman, Suzanne C, Hulshoff Pol, Hilleke E, de Geus, Eco J C, Bartels, Meike, Ropers, H Hilger, Hottenga, Jouke-Jan, Boomsma, Dorret I

المساهمون: Onderzoeksgroep 1, Brain

مصطلحات موضوعية: Adolescent, Adult, Child, Preschool, Female, Genetic Testing, Genome, Human, Humans, Infant, Intelligence, Male, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Journal Article, Research Support, N.I.H., Extramural, Non-U.S. Gov't

الوصف: Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a Mendelian disorder and a classic polygenic trait, we performed an association study to examine the effect of 43 genes implicated in autosomal recessive cognitive disorders on intelligence in an unselected Dutch population (N=1316). Using both single-nucleotide polymorphism (SNP)- and gene-based association testing, we detected an association between intelligence and the genes of interest, with genes ELP2, TMEM135, PRMT10, and RGS7 showing the strongest associations. This is a demonstration of the relevance of genes implicated in monogenic disorders of intelligence to normal-range intelligence, and a corroboration of the utility of employing knowledge on monogenic disorders in identifying the genetic variability underlying complex traits.

وصف الملف: application/pdf

العلاقة: https://dspace.library.uu.nl/handle/1874/350384Test

الإتاحة: https://dspace.library.uu.nl/handle/1874/350384Test

المؤلفون: Speliotes, Elizabeth K, Yerges-Armstrong, Laura M, Wu, Jun, Hernaez, Ruben, Kim, Lauren J, Palmer, Cameron D, Gudnason, Vilmundur, Eiriksdottir, Gudny, Garcia, Melissa E, Launer, Lenore J, Nalls, Michael A, Clark, Jeanne M, Mitchell, Braxton D, Shuldiner, Alan R, Butler, Johannah L, Tomas, Marta, Hoffmann, Udo, Hwang, Shih-Jen, Massaro, Joseph M, O'Donnell, Christopher J., Sahani, Dushyant V, Salomaa, Veikko, Schadt, Eric E, Schwartz, Stephen M, Siscovick, David S, Voight, Benjamin F, Jeffrey Carr, J., Feitosa, Mary F, Harris, Tamara B, Fox, Caroline S, Smith, Albert V, Linda Kao, W. H., Hirschhorn, Joel N, Borecki, Ingrid B, McCullough, Arthur, Bringman, Diane, Dasarathy, Srinivasan, Edwards, Kevin, Hawkins, Carol, Liu, Yao-Chang, Rogers, Nicholette, Ruth Sargent, P. A. -C., Stager, Margaret, Diehl, Anna Mae, Abdelmalek, Manal, Gottfried, Marcia, Guy, Cynthia, Killenberg, Paul, Kwan, Samantha, Pan, Yi-Ping, Piercy, Dawn, Smith, Melissa, Chalasani, Naga, Bhimalli, Prajakta, Cummings, Oscar W., Klipsch, Ann, Lee, Lydia, Molleston, Jean, Ragozzino, Linda, Vuppalanchi, Raj, Neuschwander-Tetri, Brent A., Barlow, Sarah, Derdoy, Jose, Hoffmann, Joyce, King, Debra, Siegner, Joan, Stewart, Susan, Thompson, Judy, Brunt, Elizabeth, Lavine, Joel E., Behling, Cynthia, Clark, Lisa, Durelle, Janis, Hassanein, Tarek, Petcharaporn, Lita, Schwimmer, Jeffrey B., Sirlin, Claude, Stein, Tanya, Bass, Nathan M., Bambha, Kiran, Ferrell, Linda D., Filipowski, Danuta, Merriman, Raphael, Pabst, Mark, Rosenthal, Monique, Rosenthal, Philip, Steel, Tessa, Sanyal, Arun J., Boyett, Sherry, Bryan, Daphne, Contos, Melissa J., Fuchs, Michael, Graham, Martin, Jones, Amy, Luketic, Velimir A. C., Sandhu, Bimalijit, Sargeant, Carol, Selph, Kimberly, White, Melanie, Kowdley, Kris V., Gyurkey, Grace, Mooney, Jody, Nelson, James, Roberts, Sarah, Saunders, Cheryl, Stead, Alice, Wang, Chia, Yeh, Matthew, Kleiner, David, Doo, Edward, Everhart, Jay, Hoofnagle, Jay H., Robuck, Patricia R., Seeff, Leonard, Tonascia, James, Belt, Patricia, Brancati, Fred, Colvin, Ryan, Donithan, Michele, Green, Mika, Isaacson, Milana, Kim, Wana, Miriel, Laura, Sternberg, Alice, Ünalp, Aynur, Van Natta, Mark, Wilson, Laura, Yates, Katherine, Willer, Cristen J., Berndt, Sonja I., Monda, Keri L., Thorleifsson, Gudmar, Jackson, Anne U., Allen, Hana Lango, Lindgren, Cecilia M., Luan, Jian'an, Mägi, Reedik, Randall, Joshua, Vedantam, Sailaja, Winkler, Thomas W., Qi, Lu, Workalemahu, Tsegaselassie, Heid, Iris M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Weedon, Michael N., Wheeler, Eleanor, Wood, Andrew R., Ferreira, Teresa, Weyant, Robert J., Segrè, Ayellet V., Estrada, Karol, Liang, Liming, Nemesh, James, Park, Ju-Hyun, Gustafsson, Stefan, Kilpeläinen, Tuomas O., Yang, Jian, Bouatia-Naji, Nabila, Esko, Tõnu, Kutalik, Zoltán, Mangino, Massimo, Raychaudhuri, Soumya, Scherag, Andre, Welch, Ryan, Zhao, Jing Hua, Aben, Katja K., Absher, Devin M., Amin, Najaf, Dixon, Anna L., Fisher, Eva, Glazer, Nicole L., Goddard, Michael E., Heard-Costa, Nancy L., Hoesel, Volker, Hottenga, Jouke Jan, Johansson, Åsa, Johnson, Toby, Ketkar, Shamika, Lamina, Claudia, Li, Shengxu, Moffatt, Miriam F., Myers, Richard H., Narisu, Narisu, Perry, John R. B., Peters, Marjolein J., Preuss, Michael, Ripatti, Samuli, Rivadeneira, Fernando, Sandholt, Camilla, Scott, Laura J., Timpson, Nicholas J., Tyrer, Jonathan P., van Wingerden, Sophie, Watanabe, Richard M., White, Charles C., Wiklund, Fredrik, Barlassina, Christina, Chasman, Daniel I., Cooper, Matthew N., Jansson, John-Olov, Lawrence, Robert W., Pellikka, Niina, Prokopenko, Inga, Shi, Jianxin, Thiering, Elisabeth, Alavere, Helene, Alibrandi, Maria T. S., Almgren, Peter, Arnold, Alice M., Aspelund, Thor, Atwood, Larry D., Balkau, Beverley, Balmforth, Anthony J., Bennett, Amanda J., Ben-Shlomo, Yoav, Bergman, Richard N., Bergmann, Sven, Biebermann, Heike, Blakemore, Alexandra I. F., Boes, Tanja, Bonnycastle, Lori L., Bornstein, Stefan R., Brown, Morris J., Buchanan, Thomas A., Busonero, Fabio, Campbell, Harry, Cappuccio, Francesco P., Cavalcanti-Proença, Christine, Chen, Yii-Der Ida, Chen, Chih-Mei, Chines, Peter, Clarke, Robert, Coin, Lachlan J. M., Connell, John, Day, Ian N. M., den Heijer, Martin, Duan, Jubao, Ebrahim, Shah, Elliott, Paul, Elosua, Roberto, Erdos, Michael R., Eriksson, Johan G., Facheris, Maurizio F., Felix, Stephan B., Fischer-Posovszky, Pamela, Folsom, Aaron R., Friedrich, Nele, Freimer, Nelson B., Fu, Mao, Gaget, Stefan, Gejman, Pablo V., Geus, Eco J. C., Gieger, Christian, Gjesing, Anette P., Goel, Anuj, Goyette, Philippe, Grallert, Harald, Gräβler, Jürgen, Greenawalt, Danielle M., Groves, Christopher J., Guiducci, Candace, Hartikainen, Anna-Liisa, Hassanali, Neelam, Hall, Alistair S., Havulinna, Aki S., Hayward, Caroline, Heath, Andrew C., Hengstenberg, Christian, Hicks, Andrew A., Hinney, Anke, Hofman, Albert, Homuth, Georg, Hui, Jennie, Igl, Wilmar, Iribarren, Carlos, Isomaa, Bo, Jacobs, Kevin B., Jarick, Ivonne, Jewell, Elizabeth, John, Ulrich, Jørgensen, Torben, Jousilahti, Pekka, Jula, Antti, Kaakinen, Marika, Kajantie, Eero, Kaplan, Lee M., Kathiresan, Sekar, Kettunen, Johannes, Kinnunen, Leena, Knowles, Joshua W., Kolcic, Ivana, König, Inke R., Koskinen, Seppo, Kovacs, Peter, Kuusisto, Johanna, Kraft, Peter, Kvaløy, Kirsti, Laitinen, Jaana, Lantieri, Olivier, Lanzani, Chiara, Lecoeur, Cecile, Lehtimäki, Terho, Lettre, Guillaume, Liu, Jianjun, Lokki, Marja-Liisa, Lorentzon, Mattias, Luben, Robert N., Ludwig, Barbara, Manunta, Paolo, Marek, Diana, Marre, Michel, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Anne, McKnight, Barbara, Meitinger, Thomas, Melander, Olle, Meyre, David, Midthjell, Kristian, Montgomery, Grant W., Morken, Mario A., Morris, Andrew P., Mulic, Rosanda, Ngwa, Julius S., Nelis, Mari, Neville, Matt J., Nyholt, Dale R., O'Rahilly, Stephen, Ong, Ken K., Oostra, Ben, Paré, Guillaume, Parker, Alex N., Perola, Markus, Pichler, Irene, Pietiläinen, Kirsi H., Platou, Carl G. P., Polasek, Ozren, Pouta, Anneli, Rafelt, Suzanne, Raitakari, Olli, Rayner, Nigel W., Ridderstråle, Martin, Rief, Winfried, Ruokonen, Aimo, Robertson, Neil R., Rzehak, Peter, Sanders, Alan R., Sandhu, Manjinder S., Sanna, Serena, Saramies, Jouko, Savolainen, Markku J., Scherag, Susann, Schipf, Sabine, Schreiber, Stefan, Schunkert, Heribert, Silander, Kaisa, Sinisalo, Juha, Smit, Jan H., Soranzo, Nicole, Sovio, Ulla, Stephens, Jonathan, Surakka, Ida, Swift, Amy, Tammesoo, Mari-Liis, Tardif, Jean-Claude, Teder-Laving, Maris, Teslovich, Tanya M., Thompson, John R., Thomson, Brian, Tönjes, Anke, Tuomi, Tiinamaija, van Meurs, Joyce B. J., van Ommen, Gert-Jan, Vatin, Vincent, Viikari, Jorma, Visvikis-Siest, Sophie, Vitart, Veronique, Vogel, Carla I. G., Waite, Lindsay L., Wallaschofski, Henri, Bragi Walters, G., Widen, Elisabeth, Wiegand, Susanna, Wild, Sarah H., Willemsen, Gonneke, Witte, Daniel R., Witteman, Jacqueline C., Xu, Jianfeng, Zhang, Qunyuan, Zgaga, Lina, Ziegler, Andreas, Zitting, Paavo, Beilby, John P., Farooqi, I. Sadaf, Hebebrand, Johannes, Huikuri, Heikki V., James, Alan L., Kähönen, Mika, Levinson, Douglas F., Macciardi, Fabio, Nieminen, Markku S., Ohlsson, Claes, Ridker, Paul M., Stumvoll, Michael, Beckmann, Jacques S., Boeing, Heiner, Boerwinkle, Eric, Boomsma, Dorret I., Caulfield, Mark J., Chanock, Stephen J., Adrienne Cupples, L., Smith, George Davey, Erdmann, Jeanette, Froguel, Philippe, Grönberg, Henrik, Gyllensten, Ulf, Hall, Per, Hansen, Torben, Hattersley, Andrew T., Hayes, Richard B., Heinrich, Joachim, Hu, Frank B., Hveem, Kristian, Illig, Thomas, Jarvelin, Marjo-Riitta, Kaprio, Jaakko, Karpe, Fredrik, Khaw, Kay-Tee, Kiemeney, Lambertus A., Krude, Heiko, Laakso, Markku, Lawlor, Debbie A., Metspalu, Andres, Munroe, Patricia B., Ouwehand, Willem H., Pedersen, Oluf, Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Quertermous, Thomas, Reinehr, Thomas, Rissanen, Aila, Rudan, Igor, Samani, Nilesh J., Schwarz, Peter, Spector, Timothy D., Tuomilehto, Jaakko, Uda, Manuela, Uitterlinden, André G., Valle, Timo T., Wabitsch, Martin, Waeber, Gérard, Wareham, Nicholas J., Watkins, Hugh, Wilson, James F., Wright, Alan F., Carola Zillikens, M., Chatterjee, Nilanjan, Mc, Steven A., Purcell, Shaun, Visscher, Peter M., Assimes, Themistocles L., Deloukas, Panos, Groop, Leif C., Haritunians, Talin, Hunter, David J., Kaplan, Robert C., Mohlke, Karen L., O'Connell, Jeffrey R., Peltonen, Leena, Schlessinger, David, Strachan, David P., van Duijn, Cornelia M., Wichmann, H. -Erich, Frayling, Timothy M., Thorsteinsdottir, Unnur, Abecasis, Gonçalo R., Barroso, Inês, Boehnke, Michael, Stefansson, Kari, North, Kari E., McCarthy, Mark I., Ingelsson, Erik, Loos, Ruth J. F., Dupuis, Josée, Langenberg, Claudia, Saxena, Richa, Gloyn, Anna L., Rybin, Denis, Henneman, Peter, Dehghan, Abbas, Franklin, Christopher S, Navarro, Pau, Song, Kijoung, Egan, Josephine M, Lajunen, Taina, Grarup, Niels, Sparsø, Thomas, Doney, Alex, Li, Man, Kanoni, Stavroula, Shrader, Peter, Kumari, Meena, Zabena, Carina, Rocheleau, Ghislain, An, Ping, Elliott, Amanda, McCarroll, Steven A, Payne, Felicity, Roccasecca, Rosa Maria, Pattou, François, Sethupathy, Praveen, Ardlie, Kristin, Ariyurek, Yavuz, Barter, Philip, Benediktsson, Rafn, Bochud, Murielle, Bonnefond, Amélie, Borch-Johnsen, Knut, Böttcher, Yvonne, Brunner, Eric, Bumpstead, Suzannah J, Charpentier, Guillaume, Cornelis, Marilyn, Crawford, Gabe, Crisponi, Laura, de Geus, Eco J. C., Delplanque, Jerome, Dina, Christian, 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, Hadjadj, Samy, Hallmans, Göran, Hammond, Naomi, Han, Xijing, Heath, Simon C., Hercberg, Serge, Herder, Christian, Hillman, David R., Hingorani, Aroon D., Hung, Joe, Johnson, Paul R. V., Antero Kesaniemi, Y., Kivimaki, Mika, Knight, Beatrice, Kyvik, Kirsten Ohm, Lathrop, G. Mark, Bacquer, Olivier Le, Li, Yun, Lyssenko, Valeriya, Mahley, Robert, Manning, Alisa K., Martínez-Larrad, María Teresa, McAteer, Jarred B., McCulloch, Laura J., McPherson, Ruth, Meisinger, Christa, Melzer, David, Mukherjee, Sutapa, Naitza, Silvia, Orrù, Marco, Pakyz, Ruth, Palmer, Colin N. A., Paolisso, Giuseppe, Pattaro, Cristian, Pearson, Daniel, Peden, John F., Pedersen, Nancy L., Pfeiffer, Andreas F. H., Posthuma, Danielle, Potter, Simon C., Province, Michael A., Psaty, Bruce M., Rathmann, Wolfgang, Rice, Kenneth, Roden, Michael, Rolandsson, Olov, Sandbaek, Annelli, Sayer, Avan Aihie, Scheet, Paul, Seedorf, Udo, Sharp, Stephen J., Shields, Beverley, Sigurðsson, Gunnar, Sijbrands, Eric J. G., Silveira, Angela, Simpson, Laila, Singleton, Andrew, Smith, Nicholas L., Syddall, Holly, Syvänen, Ann-Christine, Tanaka, Toshiko, Thorand, Barbara, Tichet, Jean, van Dijk, Ko Willems, van Hoek, Mandy, Varma, Dhiraj, Vogelzangs, Nicole, Wagner, Peter J, Walley, Andrew, Walters, G. Bragi, Ward, Kim L., Witteman, Jaqueline C. M., Yarnell, John W. G., Zeggini, Eleftheria, Zelenika, Diana, Zethelius, Björn, Zhai, Guangju, Zillikens, M Carola, Meneton, Pierre, Magnusson, Patrik K. E., Nathan, David M., Williams, Gordon H., Spranger, Joachim, Cooper, Cyrus, Dedoussis, George V., Lind, Lars, Morris, Andrew D., Palmer, Lyle J., Franks, Paul W., Marmot, Michael, Pankow, James S., Sampson, Michael J., Erich Wichmann, H., Hamsten, Anders, Altshuler, David, Rotter, Jerome I., Ferrucci, Luigi, Kong, Augustine, Duijn, Cornelia Mvan, Aulchenko, Yurii S., Cao, Antonio, Scuteri, Angelo, Waterworth, Dawn M, Vollenweider, Peter, Mooser, Vincent, Sladek, Robert, Meigs, James B, Florez, Jose C

المساهمون: Speliotes, Elizabeth K, Yerges-Armstrong, Laura M, Wu, Jun, Hernaez, Ruben, Kim, Lauren J, Palmer, Cameron D, Gudnason, Vilmundur, Eiriksdottir, Gudny, Garcia, Melissa E, Launer, Lenore J, Nalls, Michael A, Clark, Jeanne M, Mitchell, Braxton D, Shuldiner, Alan R, Butler, Johannah L, Tomas, Marta, Hoffmann, Udo, Hwang, Shih-Jen, Massaro, Joseph M, O'Donnell, Christopher J., Sahani, Dushyant V, Salomaa, Veikko, Schadt, Eric E, Schwartz, Stephen M, Siscovick, David S, Voight, Benjamin F, Jeffrey Carr, J., Feitosa, Mary F, Harris, Tamara B, Fox, Caroline S, Smith, Albert V, Linda Kao, W. H., Hirschhorn, Joel N, Borecki, Ingrid B, Mccullough, Arthur, Bringman, Diane, Dasarathy, Srinivasan, Edwards, Kevin, Hawkins, Carol, Liu, Yao-Chang, Rogers, Nicholette, Ruth Sargent, P. A. -C., Stager, Margaret, Diehl, Anna Mae, Abdelmalek, Manal, Gottfried, Marcia, Guy, Cynthia, Killenberg, Paul, Kwan, Samantha, Pan, Yi-Ping, Piercy, Dawn, Smith, Melissa, Chalasani, Naga, Bhimalli, Prajakta, Cummings, Oscar W., Klipsch, Ann, Lee, Lydia, Molleston, Jean, Ragozzino, Linda, Vuppalanchi, Raj, Neuschwander-Tetri, Brent A., Barlow, Sarah, Derdoy, Jose, Hoffmann, Joyce, King, Debra, Siegner, Joan, Stewart, Susan, Thompson, Judy, Brunt, Elizabeth, Lavine, Joel E., Behling, Cynthia, Clark, Lisa, Durelle, Jani, Hassanein, Tarek, Petcharaporn, Lita, Schwimmer, Jeffrey B., Sirlin, Claude, Stein, Tanya, Bass, Nathan M., Bambha, Kiran, Ferrell, Linda D., Filipowski, Danuta, Merriman, Raphael, Pabst, Mark, Rosenthal, Monique, Rosenthal, Philip, Steel, Tessa, Sanyal, Arun J., Boyett, Sherry, Bryan, Daphne, Contos, Melissa J., Fuchs, Michael, Graham, Martin, Jones, Amy, Luketic, Velimir A. C., Sandhu, Bimalijit, Sargeant, Carol, Selph, Kimberly, White, Melanie, Kowdley, Kris V.

مصطلحات موضوعية: Adaptor Proteins, Signal Transducing, Adult, Aged, 80 and over, Blood Glucose, Case-Control Studie, Chondroitin Sulfate Proteoglycan, Cohort Studie, Fatty Liver, Genome-Wide Association Study, Human, Insulin, Lectins, C-Type, Lipase, Male, Membrane Protein, Middle Aged, Mutation, Missense, Nerve Tissue Protein, Non-alcoholic Fatty Liver Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Tomography, X-Ray Computed, Ecology, Evolution

الوصف: Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (~26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ~2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10 -8 ) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000288996600006; volume:7; issue:3; firstpage:e1001324; journal:PLOS GENETICS; http://hdl.handle.net/11388/222048Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-79953745343; http://www.plosgenetics.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pgen.1001324&representation=PDFTest

الإتاحة: https://doi.org/10.1371/journal.pgen.1001324Test
http://hdl.handle.net/11388/222048Test

المؤلفون: 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, Sigurdsson, 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

المساهمون: Department of Biostatistics, Boston University School of Public Health, Massachusetts, USA.

مصطلحات موضوعية: Adolescent, Adult, Alleles, Blood Glucose, Child, DNA Copy Number Variations, Databases, Genetic, Diabetes Mellitus, Type 2, Fasting, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeostasis, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Reproducibility of Results

الوصف: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field ; 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.

العلاقة: http://dx.doi.org/10.1038/ng.520Test; Nat. Genet. 2010, 42(2):105-16; http://hdl.handle.net/2336/93938Test; Nature genetics

الإتاحة: https://doi.org/10.1038/ng.520Test
http://hdl.handle.net/2336/93938Test

المؤلفون: Willer, Cristen J, Speliotes, Elizabeth K, Loos, Ruth J F, Li, Shengxu, 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, Qi, Lu, Randall, Joshua C, Roccasecca, Rosa Maria, Sanna, Serena, Scheet, Paul, Weedon, Michael N, Wheeler, Eleanor, Zhao, Jing Hua, Jacobs, Leonie C, Prokopenko, Inga, Soranzo, Nicole, Tanaka, Toshiko, Timpson, Nicholas J, Almgren, Peter, Bennett, Amanda, Bergman, Richard N, Bingham, Sheila A

المصدر: Nature Genetics, 41(1)

مصطلحات موضوعية: Anthropometry, Humans, Central Nervous System, Polymorphism, Single Nucleotide, Quantitative Trait, Genetic Predisposition to Disease, Cohort Studies, Alleles, Heritable, Gene Dosage, Body Weight, Colaus Study, Obesity, Genome-Wide Association Study, Quantitative Trait Loci, Body Mass Index, Meta-Analysis as Topic

الوصف: 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.

العلاقة: https://doi.org/10.17615/kr0j-1k09Test; https://cdr.lib.unc.edu/downloads/zp38wm65s?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/zp38wm65sTest

الإتاحة: https://doi.org/10.17615/kr0j-1k09Test
https://cdr.lib.unc.edu/downloads/zp38wm65s?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/zp38wm65sTest

المؤلفون: Kathiresan, Sekar, Willer, Cristen J, Peloso, Gina M, Demissie, Serkalem, Musunuru, Kiran, Schadt, Eric E, Kaplan, Lee, Bennett, Derrick, Li, Yun, Tanaka, Toshiko, Voight, Benjamin F, Bonnycastle, Lori L, Jackson, Anne U, Crawford, Gabriel, Surti, Aarti, Guiducci, Candace, Burtt, Noel P, Parish, Sarah, Clarke, Robert, Zelenika, Diana, Kubalanza, Kari A, Morken, Mario A, Scott, Laura J, Stringham, Heather M, Galan, Pilar, Swift, Amy J, Kuusisto, Johanna, Bergman, Richard N, Sundvall, Jouko, Laakso, Markku, Ferrucci, Luigi, Scheet, Paul

المصدر: Nature Genetics, 41(1)

مصطلحات موضوعية: Liver, Alleles, Humans, Adult, Meta-Analysis as Topic, Phenotype, Syndrome, Female, Cholesterol, HDL, Male, Quantitative Trait Loci, Triglycerides, Gene Expression Regulation, Reproducibility of Results, Dyslipidemias, RNA, Messenger, Polymorphism, Single Nucleotide, Middle Aged, Multifactorial Inheritance, LDL, Genome-Wide Association Study

الوصف: Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 × 10-8), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10-15 for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.

العلاقة: https://doi.org/10.17615/wktm-vc19Test; https://cdr.lib.unc.edu/downloads/1r66j809w?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/1r66j809wTest

الإتاحة: https://doi.org/10.17615/wktm-vc19Test
https://cdr.lib.unc.edu/downloads/1r66j809w?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/1r66j809wTest

المؤلفون: Prokopenko, Inga, Langenberg, Claudia, Florez, Jose C., Saxena, Richa, Soranzo, Nicole, Thorleifsson, Gudmar, Loos, Ruth J.F., Manning, Alisa K., Jackson, Anne U., Aulchenko, Yurii, Potter, Simon C., Erdos, Michael R., Sanna, Serena, Hottenga, Jouke-Jan, Wheeler, Eleanor, Kaakinen, Marika, Lyssenko, Valeriya, Chen, Wei-Min, Ahmadi, Kourosh, Beckmann, Jacques S., Bergman, Richard N., Bochud, Murielle, Bonnycastle, Lori L., Buchanan, Thomas A., Cao, Antonio, Cervino, Alessandra, Coin, Lachlan, Collins, Francis S., Crisponi, Laura, de Geus, Eco JC, Dehghan, Abbas, Deloukas, Panos, Doney, Alex S F, Elliott, Paul, Freimer, Nelson, Gateva, Vesela, Herder, Christian, Hofman, Albert, Hughes, Thomas E., Hunt, Sarah, Illig, Thomas, Inouye, Michael, Isomaa, Bo, Johnson, Toby, Kong, Augustine, Krestyaninova, Maria, Kuusisto, Johanna, Laakso, Markku, Lim, Noha, Lindblad, Ulf, Lindgren, Cecilia M., McCann, Owen T., Mohlke, Karen L., Morris, Andrew D, Naitza, Silvia, Orrù, Marco, Palmer, Colin N A, Pouta, Anneli, Randall, Joshua, Rathmann, Wolfgang, Saramies, Jouko, Scheet, Paul, Scott, Laura J., Scuteri, Angelo, Sharp, Stephen, Sijbrands, Eric, Smit, Jan H., Song, Kijoung, Steinthorsdottir, Valgerdur, Stringham, Heather M., Tuomi, Tiinamaija, Tuomilehto, Jaakko, Uitterlinden, André G., Voight, Benjamin F., Waterworth, Dawn, Wichmann, H.-Erich, Willemsen, Gonneke, Witteman, Jacqueline CM, Yuan, Xin, Zhao, Jing Hua, Zeggini, Eleftheria, Schlessinger, David, Sandhu, Manjinder, Boomsma, Dorret I, Uda, Manuela, Spector, Tim D., Penninx, Brenda WJH, Altshuler, David, Vollenweider, Peter, Jarvelin, Marjo Riitta, Lakatta, Edward, Waeber, Gerard, Fox, Caroline S., Peltonen, Leena, Groop, Leif C., Mooser, Vincent, Cupples, L. Adrienne, Thorsteinsdottir, Unnur, Boehnke, Michael, Barroso, Inês, Van Duijn, Cornelia, Dupuis, Josée, Watanabe, Richard M., Stefansson, Kari, McCarthy, Mark I., Wareham, Nicholas J., Meigs, James B., Abecasis, Goncalo R.

مصطلحات موضوعية: Blood Glucose, Diabetes Mellitus, Type 2, Meta-Analysis as Topic, Receptor, Melatonin, MT2, Case-Control Studies, Quantitative Trait Loci, Receptors, Melatonin, Humans, Genetic Predisposition to Disease, Fasting, Polymorphism, Single Nucleotide, Article, Genome-Wide Association Study

الوصف: To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::debdb899b25512a22179f90a67bbd91cTest
https://europepmc.org/articles/PMC2682768Test/