جهت دسترسی به کاربرگه ی زیر، از این لینک استفاده کنید. http://192.168.1.35:80/jspui/handle/Hannan/19409
Title: Genetic fine-mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci
Authors: Gaulton, Kyle J;Ferreira, Teresa;Lee, Yeji;Raimondo, Anne;Mägi, Reedik;Reschen, Michael E;Mahajan, Anubha;Locke, Adam;Rayner, N William;Robertson, Neil;Scott, Robert A;Prokopenko, Inga;Scott, Laura J;Green, Todd;Sparso, Thomas;Thuillier, Dorothee;Yengo, Loic;Grallert, Harald;Wahl, Simone;Frånberg, Mattias;Strawbridge, Rona J;Kestler, Hans;Chheda, Himanshu;Eisele, Lewin;Gustafsson, Stefan;Steinthorsdottir, Valgerdur;Thorleifsson, Gudmar;Qi, Lu;Karssen, Lennart C;van Leeuwen, Elisabeth M;Willems, Sara M;Li, Man;Chen, Han;Fuchsberger, Christian;Kwan, Phoenix;Ma, Clement;Linderman, Michael;Lu, Yingchang;Thomsen, Soren K;Rundle, Jana K;Beer, Nicola L;van de Bunt, Martijn;Chalisey, Anil;Kang, Hyun Min;Voight, Benjamin F;Abecasis, Goncalo R;Almgren, Peter;Baldassarre, Damiano;Balkau, Beverley;Benediktsson, Rafn;Blüher, Matthias;Boeing, Heiner;Bonnycastle, Lori L;Borringer, Erwin P;Burtt, Noël P;Carey, Jason;Charpentier, Guillaume;Chines, Peter S;Cornelis, Marilyn C;Couper, David J;Crenshaw, Andrew T;van Dam, Rob M;Doney, Alex SF;Dorkhan, Mozhgan;Edkins, Sarah;Eriksson, Johan G;Esko, Tonu;Eury, Elodie;Fadista, João;Flannick, Jason;Fontanillas, Pierre;Fox, Caroline;Franks, Paul W;Gertow, Karl;Gieger, Christian;Gigante, Bruna;Gottesman, Omri;Grant, George B;Grarup, Niels;Groves, Christopher J;Hassinen, Maija;Have, Christian T;Herder, Christian;Holmen, Oddgeir L;Hreidarsson, Astradur B;Humphries, Steve E;Hunter, David J;Jackson, Anne U;Jonsson, Anna;Jørgensen, Marit E;Jørgensen, Torben;Kao, Wen-Hong L;Kerrison, Nicola D;Kinnunen, Leena;Klopp, Norman;Kong, Augustine;Kovacs, Peter;Kraft, Peter;Kravic, Jasmina;Langford, Cordelia;Leander, Karin;Liang, Liming;Lichtner, Peter;Lindgren, Cecilia M;Lindholm, Eero;Linneberg, Allan;Liu, Ching-Ti;Lobbens, Stéphane;Luan, Jian’an;Lyssenko, Valeriya;Mӓnnistö, Satu;McLeod, Olga;Meyer, Julia;Mihailov, Evelin;Mirza, Ghazala;Mühleisen, Thomas W;Müller-Nurasyid, Martina;Navarro, Carmen;Nöthen, Markus M;Oskolkov, Nikolay N;Owen, Katharine R;Palli, Domenico;Pechlivanis, Sonali;Peltonen, Leena;Perry, John RB;Platou, Carl GP;Roden, Michael;Ruderfer, Douglas;Rybin, Denis;van der Schouw, Yvonne T;Sennblad, Bengt;Sigurđsson, Gunnar;Stančáková, Alena;Steinbach, Gerald;Storm, Petter;Strauch, Konstantin;Stringham, Heather M;Sun, Qi;Thorand, Barbara;Tikkanen, Emmi;Tonjes, Anke;Trakalo, Joseph;Tremoli, Elena;Tuomi, Tiinamaija;Wennauer, Roman;Wiltshire, Steven;Wood, Andrew R;Zeggini, Eleftheria;Dunham, Ian;Birney, Ewan;Pasquali, Lorenzo;Ferrer, Jorge;Loos, Ruth JF;Dupuis, Josée;Florez, Jose C;Boerwinkle, Eric;Pankow, James S;van Duijn, Cornelia;Sijbrands, Eric;Meigs, James B;Hu, Frank B;Thorsteinsdottir, Unnur;Stefansson, Kari;Lakka, Timo A;Rauramaa, Rainer;Stumvoll, Michael;Pedersen, Nancy L;Lind, Lars;Keinanen-Kiukaanniemi, Sirkka M;Korpi-Hyövӓlti, Eeva;Saaristo, Timo E;Saltevo, Juha;Kuusisto, Johanna;Laakso, Markku;Metspalu, Andres;Erbel, Raimund;Jöckel, Karl-Heinz;Moebus, Susanne;Ripatti, Samuli;Salomaa, Veikko;Ingelsson, Erik;Boehm, Bernhard O;Bergman, Richard N;Collins, Francis S;Mohlke, Karen L;Koistinen, Heikki;Tuomilehto, Jaakko;Hveem, Kristian;Njølstad, Inger;Deloukas, Panagiotis;Donnelly, Peter J;Frayling, Timothy M;Hattersley, Andrew T;de Faire, Ulf;Hamsten, Anders;Illig, Thomas;Peters, Annette;Cauchi, Stephane;Sladek, Rob;Froguel, Philippe;Hansen, Torben;Pedersen, Oluf;Morris, Andrew D;Palmer, Collin NA;Kathiresan, Sekar;Melander, Olle;Nilsson, Peter M;Groop, Leif C;Barroso, Inês;Langenberg, Claudia;Wareham, Nicholas J;O’Callaghan, Christopher A;Gloyn, Anna L;Altshuler, David;Boehnke, Michael;Teslovich, Tanya M;McCarthy, Mark I;Morris, Andrew P
Issue Date: 2015
Description: We performed fine-mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in/near KCNQ1. “Credible sets” of variants most likely to drive each distinct signal mapped predominantly to non-coding sequence, implying that T2D association is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine-mapping implicated rs10830963 as driving T2D association. We confirmed that this T2D-risk allele increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D-risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
URI: http://192.168.1.35:80/jspui/handle/Hannan/19409
Other Identifiers: Gaulton, K. J., T. Ferreira, Y. Lee, A. Raimondo, R. Mägi, M. E. Reschen, A. Mahajan, et al. 2015. “Genetic fine-mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.” Nature genetics 47 (12): 1415-1425. doi:10.1038/ng.3437. http://dx.doi.org/10.1038/ng.3437.
1061-4036
http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320459
Type Of Material: Journal Article
Appears in Collections:Harvard T.H. Chan School of Public Health

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