Progress in the genetics of common obesity and type 2 diabetes

被引:63
作者
Vimaleswaran, Karani S. [1 ]
Loos, Ruth J. F. [1 ]
机构
[1] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge CB2 0QQ, England
来源
EXPERT REVIEWS IN MOLECULAR MEDICINE | 2010年 / 12卷
基金
英国医学研究理事会;
关键词
GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; MELANOCORTIN-4 RECEPTOR GENE; ENDOPLASMIC-RETICULUM STRESS; ENPP1 K121Q POLYMORPHISM; NEUROTROPHIC FACTOR BDNF; FASTING GLUCOSE-LEVELS; LOW PHYSICAL-ACTIVITY; FTO GENE; INSULIN-RESISTANCE;
D O I
10.1017/S1462399410001389
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The prevalence of obesity and diabetes, which are heritable traits that arise from the interactions of multiple genes and lifestyle factors, continues to rise worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past 15 years, candidate gene and genome-wide linkage studies have been the main genetic epidemiological approaches to identify genetic loci for obesity and diabetes, yet progress has been slow and success limited. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries. Genome-wide association is a hypothesis-generating approach that aims to identify new loci associated with the disease or trait of interest. So far, three waves of large-scale genome-wide association studies have identified 19 loci for common obesity and 18 for common type 2 diabetes. Although the combined contribution of these loci to the variation in obesity and diabetes risk is small and their predictive value is typically low, these recently identified loci are set to substantially improve our insights into the pathophysiology of obesity and diabetes. This will require integration of genetic epidemiological methods with functional genomics and proteomics. However, the use of these novel insights for genetic screening and personalised treatment lies some way off in the future.
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页数:27
相关论文
共 123 条
[1]  
Allison DB, 1996, INT J OBESITY, V20, P501
[2]   AMINO-ACID POLYMORPHISMS OF INSULIN-RECEPTOR SUBSTRATE-1 IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS [J].
ALMIND, K ;
BJORBAEK, C ;
VESTERGAARD, H ;
HANSEN, T ;
ECHWALD, S ;
PEDERSEN, O .
LANCET, 1993, 342 (8875) :828-832
[3]   The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes [J].
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 .
NATURE GENETICS, 2000, 26 (01) :76-80
[4]   Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation [J].
Andreasen, Camilla H. ;
Stender-Petersen, Kirstine L. ;
Mogensen, Mette S. ;
Torekov, Signe S. ;
Wegner, Lise ;
Andersen, Gitte ;
Nielsen, Arne L. ;
Albrechtsen, Anders ;
Borch-Johnsen, Knut ;
Rasmussen, Signe S. ;
Clausen, Jesper O. ;
Sandbaek, Annelli ;
Lauritzen, Torsten ;
Hansen, Lars ;
Jorgensen, Torben ;
Pedersen, Oluf ;
Hansen, Torben .
DIABETES, 2008, 57 (01) :95-101
[5]   Candidate gene association study in type 2 diabetes indicates a role for genes involved in β-cell function as well as insulin action [J].
Barroso, I ;
Luan, J ;
Middelberg, RPS ;
Harding, AH ;
Franks, PW ;
Jakes, RW ;
Clayton, D ;
Schafer, AJ ;
O'Rahilly, S ;
Wareham, NJ .
PLOS BIOLOGY, 2003, 1 (01) :41-55
[6]   Common nonsynonymous variants in PCSK1 confer risk of obesity [J].
Benzinou, Michael ;
Creemers, John W. M. ;
Choquet, Helene ;
Lobbens, Stephane ;
Dina, Christian ;
Durand, Emmanuelle ;
Guerardel, Audrey ;
Boutin, Philippe ;
Jouret, Beatrice ;
Heude, Barbara ;
Balkau, Beverley ;
Tichet, Jean ;
Marre, Michel ;
Potoczna, Natascha ;
Horber, Fritz ;
Le Stunff, Catherine ;
Czernichow, Sebastien ;
Sandbaek, Annelli ;
Lauritzen, Torsten ;
Borch-Johnsen, Knut ;
Andersen, Gitte ;
Kiess, Wieland ;
Koerner, Antje ;
Kovacs, Peter ;
Jacobson, Peter ;
Carlsson, Lena M. S. ;
Walley, Andrew J. ;
Jorgensen, Torben ;
Hansen, Torben ;
Pedersen, Oluf ;
Meyre, David ;
Froguel, Philippe .
NATURE GENETICS, 2008, 40 (08) :943-945
[7]   Endocannabinoid receptor 1 gene variations increase risk for obesity and modulate body mass index in European populations [J].
Benzinou, Michael ;
Chevre, Jean-Claude ;
Ward, Kirsten J. ;
Lecoeur, Cecile ;
Dina, Christian ;
Lobbens, Stephane ;
Durand, Emmanuelle ;
Delplanque, Jerome ;
Horber, Fritz F. ;
Heude, Barbara ;
Balkau, Beverley ;
Borch-Johnsen, Knut ;
Jorgensen, Torben ;
Hansen, Torben ;
Pedersen, Oluf ;
Meyre, David ;
Froguel, Philippe .
HUMAN MOLECULAR GENETICS, 2008, 17 (13) :1916-1921
[8]   A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels [J].
Bouatia-Naji, Nabila ;
Rocheleau, Ghislain ;
Van Lommel, Leentje ;
Lemaire, Katleen ;
Schuit, Frans ;
Cavalcanti-Proenca, Christine ;
Marchand, Marion ;
Hartikainen, Anna-Liisa ;
Sovio, Ulla ;
De Graeve, Franck ;
Rung, Johan ;
Vaxillaire, Martine ;
Tichet, Jean ;
Marre, Michel ;
Balkau, Beverley ;
Weill, Jacques ;
Elliott, Paul ;
Jarvelin, Marjo-Riitta ;
Meyre, David ;
Polychronakos, Constantin ;
Dina, Christian ;
Sladek, Robert ;
Froguel, Philippe .
SCIENCE, 2008, 320 (5879) :1085-1088
[9]   A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk [J].
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 .
NATURE GENETICS, 2009, 41 (01) :89-94
[10]   Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].
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. .
NATURE, 2007, 447 (7145) :661-678