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
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
收藏
页码:132 / 140
页数:9
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  • [1] A haplotype map of the human genome
    Altshuler, D
    Brooks, LD
    Chakravarti, A
    Collins, FS
    Daly, MJ
    Donnelly, P
    Gibbs, RA
    Belmont, JW
    Boudreau, A
    Leal, SM
    Hardenbol, P
    Pasternak, S
    Wheeler, DA
    Willis, TD
    Yu, FL
    Yang, HM
    Zeng, CQ
    Gao, Y
    Hu, HR
    Hu, WT
    Li, CH
    Lin, W
    Liu, SQ
    Pan, H
    Tang, XL
    Wang, J
    Wang, W
    Yu, J
    Zhang, B
    Zhang, QR
    Zhao, HB
    Zhao, H
    Zhou, J
    Gabriel, SB
    Barry, R
    Blumenstiel, B
    Camargo, A
    Defelice, M
    Faggart, M
    Goyette, M
    Gupta, S
    Moore, J
    Nguyen, H
    Onofrio, RC
    Parkin, M
    Roy, J
    Stahl, E
    Winchester, E
    Ziaugra, L
    Shen, Y
    [J]. NATURE, 2005, 437 (7063) : 1299 - 1320
  • [2] The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes
    Altshuler, D
    Hirschhorn, JN
    Klannemark, M
    Lindgren, CM
    Vohl, MC
    Nemesh, J
    Lane, CR
    Schaffner, SF
    Bolk, S
    Brewer, C
    Tuomi, T
    Gaudet, D
    Hudson, TJ
    Daly, M
    Groop, L
    Lander, ES
    [J]. NATURE GENETICS, 2000, 26 (01) : 76 - 80
  • [3] [Anonymous], TODAY SCI HIST
  • [4] A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk
    Bouatia-Naji, Nabila
    Bonnefond, Amelie
    Cavalcanti-Proenca, Christine
    Sparso, Thomas
    Holmkvist, Johan
    Marchand, Marion
    Delplanque, Jerome
    Lobbens, Stephane
    Rocheleau, Ghislain
    Durand, Emmanuelle
    De Graeve, Franck
    Chevre, Jean-Claude
    Borch-Johnsen, Knut
    Hartikainen, Anna-Liisa
    Ruokonen, Aimo
    Tichet, Jean
    Marre, Michel
    Weill, Jacques
    Heude, Barbara
    Tauber, Maithe
    Lemaire, Katleen
    Schuit, Frans
    Elliott, Paul
    Jorgensen, Torben
    Charpentier, Guillaume
    Hadjadj, Samy
    Cauchi, Stephane
    Vaxillaire, Martine
    Sladek, Robert
    Visvikis-Siest, Sophie
    Balkau, Beverley
    Levy-Marchal, Claire
    Pattou, Francois
    Meyre, David
    Blakemore, Alexandra I. F.
    Jarvelin, Marjo-Riita
    Walley, Andrew J.
    Hansen, Torben
    Dina, Christian
    Pedersen, Oluf
    Froguel, Philippe
    [J]. NATURE GENETICS, 2009, 41 (01) : 89 - 94
  • [5] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
    Burton, Paul R.
    Clayton, David G.
    Cardon, Lon R.
    Craddock, Nick
    Deloukas, Panos
    Duncanson, Audrey
    Kwiatkowski, Dominic P.
    McCarthy, Mark I.
    Ouwehand, Willem H.
    Samani, Nilesh J.
    Todd, John A.
    Donnelly, Peter
    Barrett, Jeffrey C.
    Davison, Dan
    Easton, Doug
    Evans, David
    Leung, Hin-Tak
    Marchini, Jonathan L.
    Morris, Andrew P.
    Spencer, Chris C. A.
    Tobin, Martin D.
    Attwood, Antony P.
    Boorman, James P.
    Cant, Barbara
    Everson, Ursula
    Hussey, Judith M.
    Jolley, Jennifer D.
    Knight, Alexandra S.
    Koch, Kerstin
    Meech, Elizabeth
    Nutland, Sarah
    Prowse, Christopher V.
    Stevens, Helen E.
    Taylor, Niall C.
    Walters, Graham R.
    Walker, Neil M.
    Watkins, Nicholas A.
    Winzer, Thilo
    Jones, Richard W.
    McArdle, Wendy L.
    Ring, Susan M.
    Strachan, David P.
    Pembrey, Marcus
    Breen, Gerome
    St Clair, David
    Caesar, Sian
    Gordon-Smith, Katherine
    Jones, Lisa
    Fraser, Christine
    Green, Elain K.
    [J]. NATURE, 2007, 447 (7145) : 661 - 678
  • [6] Dabelea D, 2001, J PEDIATR ENDOCR MET, V14, P1085
  • [7] Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects
    DeBaun, MR
    Niemitz, EL
    McNeil, DE
    Brandenburg, SA
    Lee, MP
    Feinberg, AP
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (03) : 604 - 611
  • [8] New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
    Dupuis, Josee
    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.
    Magi, 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
    Sparso, Thomas
    Doney, Alex
    Voight, Benjamin F.
    Stringham, Heather M.
    Li, Man
    Kanoni, Stavroula
    Shrader, Peter
    Cavalcanti-Proenca, 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
    [J]. NATURE GENETICS, 2010, 42 (02) : 105 - U32
  • [9] Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young
    Ellard, S.
    Bellanne-Chantelot, C.
    Hattersley, A. T.
    [J]. DIABETOLOGIA, 2008, 51 (04) : 546 - 553
  • [10] Genomic Medicine: Genomic Medicine -- An Updated Primer.
    Feero, W. Gregory
    Guttmacher, Alan E.
    Collins, Francis S.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (21) : 2001 - 2011