Dorothy Hodgkin Lecture 2010 From hype to hope? A journey through the genetics of Type 2 diabetes

被引：10

作者：

McCarthy, M. I. ^{[1
,2
]}

机构：

[1] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Wellcome Trust Ctr Human Genet, Oxford OX3 7LJ, England

[2] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England

来源：

DIABETIC MEDICINE | 2011年 / 28卷 / 02期

基金：

英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

association; genetics; genome-wide association studies; physiology; Type; 2; diabetes; GENOME-WIDE ASSOCIATION; LARGE-SCALE ASSOCIATION; BIRTH-WEIGHT; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; COMPLEX DISEASES; COMMON VARIANT; GLUCOSE-LEVELS; FTO GENE; RISK;

D O I：

10.1111/j.1464-5491.2010.03194.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

P>Recent advances in genetic analysis have enabled researchers to perform genome-wide surveys for common DNA sequence variants associated with risk of Type 2 diabetes and related traits. Over the past 4 years, these endeavours have extended the number of proven Type 2 diabetes-susceptibility loci from a handful to the current total of over 40. Each of these loci provides an opportunity to uncover insights into the biology of glucose regulation and the pathogenesis of Type 2 diabetes, insights which should support clinical translation to identify novel ways of treating and preventing disease. Here, I describe (i) progress in identification of diabetes-susceptibility loci; (ii) biological insights that have been gained in the relatively short period since these loci were discovered; and (iii) the challenges that need to be addressed if we are to maximize the translational benefits of this research.

引用

页码：132 / 140

页数：9

共 50 条

[31] Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion
Lyssenko, Valeriya
Nagorny, Cecilia L. F.
Erdos, Michael R.
Wierup, Nils
Jonsson, Anna
Spegel, Peter
Bugliani, Marco
Saxena, Richa
Fex, Malin
Pulizzi, Nicolo
Isomaa, Bo
Tuomi, Tiinamaija
Nilsson, Peter
Kuusisto, Johanna
Tuomilehto, Jaakko
Boehnke, Michael
Altshuler, David
Sundler, Frank
Eriksson, Johan G.
Jackson, Anne U.
Laakso, Markku
Marchetti, Piero
Watanabe, Richard M.
Mulder, Hindrik
Groop, Leif
[J]. NATURE GENETICS, 2009, 41 (01) : 82 - 88
[32] Finding the missing heritability of complex diseases
Manolio, Teri A.
Collins, Francis S.
Cox, Nancy J.
Goldstein, David B.
Hindorff, Lucia A.
Hunter, David J.
McCarthy, Mark I.
Ramos, Erin M.
Cardon, Lon R.
Chakravarti, Aravinda
Cho, Judy H.
Guttmacher, Alan E.
Kong, Augustine
Kruglyak, Leonid
Mardis, Elaine
Rotimi, Charles N.
Slatkin, Montgomery
Valle, David
Whittemore, Alice S.
Boehnke, Michael
Clark, Andrew G.
Eichler, Evan E.
Gibson, Greg
Haines, Jonathan L.
Mackay, Trudy F. C.
McCarroll, Steven A.
Visscher, Peter M.
[J]. NATURE, 2009, 461 (7265) : 747 - 753
[33] Genome-wide association studies for complex traits: consensus, uncertainty and challenges
McCarthy, Mark I.
Abecasis, Goncalo R.
Cardon, Lon R.
Goldstein, David B.
Little, Julian
Ioannidis, John P. A.
Hirschhorn, Joel N.
[J]. NATURE REVIEWS GENETICS, 2008, 9 (05) : 356 - 369
[34] Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family:: Identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF
Pasmant, Eric
Laurendeau, Ingrid
Heron, Delphine
Vidaud, Michel
Vidaud, Dominique
Bieche, Ivan
[J]. CANCER RESEARCH, 2007, 67 (08) : 3963 - 3969
[35] Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations
Pearson, Ewan R.
Flechtner, Isabelle
Njolstad, Pal R.
Malecki, Maciej T.
Flanagan, Sarah E.
Larkin, Brian
Ashcroft, Frances M.
Klimes, Iwar
Codner, Ethel
Iotova, Violeta
Slingerland, Annabelle S.
Shield, Julian
Robert, Jean-Jacques
Holst, Jens J.
Clark, Penny M.
Ellard, Sian
Sovik, Oddmund
Polak, Michel
Hattersley, Andrew T.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (05) : 467 - 477
[36] Variants in MTNR1B influence fasting glucose levels
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 J. C.
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
[J]. NATURE GENETICS, 2009, 41 (01) : 77 - 81
[37] Genetic variants at 2q24 are associated with susceptibility to type 2 diabetes
Qi, Lu
Cornelis, Marilyn C.
Kraft, Peter
Stanya, Kristopher J.
Kao, W. H. Linda
Pankow, James S.
Dupuis, Josee
Florez, Jose C.
Fox, Caroline S.
Pare, Guillaume
Sun, Qi
Girman, Cynthia J.
Laurie, Cathy C.
Mirel, Daniel B.
Manolio, Teri A.
Chasman, Daniel I.
Boerwinkle, Eric
Ridker, Paul M.
Hunter, David J.
Meigs, James B.
Lee, Chih-Hao
van Dam, Rob M.
Hu, Frank B.
[J]. HUMAN MOLECULAR GENETICS, 2010, 19 (13) : 2706 - 2715
[38] Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia
Rung, Johan
Cauchi, Stephane
Albrechtsen, Anders
Shen, Lishuang
Rocheleau, Ghislain
Cavalcanti-Proenca, Christine
Bacot, Francois
Balkau, Beverley
Belisle, Alexandre
Borch-Johnsen, Knut
Charpentier, Guillaume
Dina, Christian
Durand, Emmanuelle
Elliott, Paul
Hadjadj, Samy
Jaervelin, Marjo-Riitta
Laitinen, Jaana
Lauritzen, Torsten
Marre, Michel
Mazur, Alexander
Meyre, David
Montpetit, Alexandre
Pisinger, Charlotta
Posner, Barry
Poulsen, Pernille
Pouta, Anneli
Prentki, Marc
Ribel-Madsen, Rasmus
Ruokonen, Aimo
Sandbaek, Anelli
Serre, David
Tichet, Jean
Vaxillaire, Martine
Wojtaszewski, Jorgen F. P.
Vaag, Allan
Hansen, Torben
Polychronakos, Constantin
Pedersen, Oluf
Froguel, Philippe
Sladek, Robert
[J]. NATURE GENETICS, 2009, 41 (10) : 1110 - U89
[39] Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
Saxena, Richa
Voight, Benjamin F.
Lyssenko, Valeriya
Burtt, Noel P.
de Bakker, Paul I. W.
Chen, Hong
Roix, Jeffrey J.
Kathiresan, Sekar
Hirschhorn, Joel N.
Daly, Mark J.
Hughes, Thomas E.
Groop, Leif
Altshuler, David
Almgren, Peter
Florez, Jose C.
Meyer, Joanne
Ardlie, Kristin
Bostroem, Kristina Bengtsson
Isomaa, Bo
Lettre, Guillaume
Lindblad, Ulf
Lyon, Helen N.
Melander, Olle
Newton-Cheh, Christopher
Nilsson, Peter
Orho-Melander, Marju
Rastam, Lennart
Speliotes, Elizabeth K.
Taskinen, Marja-Riitta
Tuomi, Tiinamaija
Guiducci, Candace
Berglund, Anna
Carlson, Joyce
Gianniny, Lauren
Hackett, Rachel
Hall, Liselotte
Holmkvist, Johan
Laurila, Esa
Sjoegren, Marketa
Sterner, Maria
Surti, Aarti
Svensson, Margareta
Svensson, Malin
Tewhey, Ryan
Blumenstiel, Brendan
Parkin, Melissa
DeFelice, Matthew
Barry, Rachel
Brodeur, Wendy
Camarata, Jody
[J]. SCIENCE, 2007, 316 (5829) : 1331 - 1336
[40] A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Scott, Laura J.
Mohlke, Karen L.
Bonnycastle, Lori L.
Willer, Cristen J.
Li, Yun
Duren, William L.
Erdos, Michael R.
Stringham, Heather M.
Chines, Peter S.
Jackson, Anne U.
Prokunina-Olsson, Ludmila
Ding, Chia-Jen
Swift, Amy J.
Narisu, Narisu
Hu, Tianle
Pruim, Randall
Xiao, Rui
Li, Xiao-Yi
Conneely, Karen N.
Riebow, Nancy L.
Sprau, Andrew G.
Tong, Maurine
White, Peggy P.
Hetrick, Kurt N.
Barnhart, Michael W.
Bark, Craig W.
Goldstein, Janet L.
Watkins, Lee
Xiang, Fang
Saramies, Jouko
Buchanan, Thomas A.
Watanabe, Richard M.
Valle, Timo T.
Kinnunen, Leena
Abecasis, Gonalo R.
Pugh, Elizabeth W.
Doheny, Kimberly F.
Bergman, Richard N.
Tuomilehto, Jaakko
Collins, Francis S.
Boehnke, Michael
[J]. SCIENCE, 2007, 316 (5829) : 1341 - 1345

← 1 2 3 4 5 →