The Genetic and Epigenetic Basis of Type 2 Diabetes and Obesity

被引：157

作者：

Drong, A. W. ^{[1
]}

Lindgren, C. M. ^{[1
]}

McCarthy, M. I. ^{[1
,2
,3
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[2] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[3] Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2012年 / 92卷 / 06期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; LARGE-SCALE ASSOCIATION; SUSCEPTIBILITY LOCI; FTO GENE; RHEUMATOID-ARTHRITIS; MISSING HERITABILITY; TRIGLYCERIDE LEVELS; COMMON VARIANTS; HUMAN-DISEASES;

D O I：

10.1038/clpt.2012.149

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Type 2 diabetes (T2D) and obesity are complex disorders that constitute major public health problems. The evidence for familial aggregation of both T2D and obesity is substantial. To date, more than 150 genetic loci are associated with the development of monogenic, syndromic, or multifactorial forms of T2D or obesity. However, the proportion of overall trait variance explained by these associated loci is modest (similar to 5-10% for T2D, similar to 2% for body mass index (BMI)). Some of the familial aggregation not attributable to known genetic variation, as well as many of the effects of environmental exposures, may reflect epigenetic processes. In this review, we discuss the evidence concerning the genetic contribution to individual risk of T2D and obesity, and explore the potential role of epigenetic mechanisms. We also explain how genetics, epigenetics, and environment are likely to interact to define the individual risk of disease.

引用

页码：707 / 715

页数：9

共 76 条

[1] Genome wide analysis reveals association of a FTO gene variant with epigenetic changes [J].

Almen, Markus Sallman ;

Jacobsson, Josefin A. ;

Moschonis, George ;

Benedict, Christian ;

Chrousos, George P. ;

Fredriksson, Robert ;

Schioth, Helgi B. .

GENOMICS, 2012, 99 (03) :132-137

[2] 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

[3] Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome [J].

Ansley, SJ ;

Badano, JL ;

Blacque, OE ;

Hill, J ;

Hoskins, BE ;

Leitch, CC ;

Kim, JC ;

Ross, AJ ;

Eichers, ER ;

Teslovich, TM ;

Mah, AK ;

Johnsen, RC ;

Cavender, JC ;

Lewis, RA ;

Leroux, MR ;

Beales, PL ;

Katsanis, N .

NATURE, 2003, 425 (6958) :628-633

[4] The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver [J].

Beer, Nicola L. ;

Tribble, Nicholas D. ;

McCulloch, Laura J. ;

Roos, Charlotta ;

Johnson, Paul R. V. ;

Orho-Melander, Marju ;

Gloyn, Anna L. .

HUMAN MOLECULAR GENETICS, 2009, 18 (21) :4081-4088

[5] Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus [J].

Bell, Christopher G. ;

Finer, Sarah ;

Lindgren, Cecilia M. ;

Wilson, Gareth A. ;

Rakyan, Vardhman K. ;

Teschendorff, Andrew E. ;

Akan, Pelin ;

Stupka, Elia ;

Down, Thomas A. ;

Prokopenko, Inga ;

Morison, Ian M. ;

Mill, Jonathan ;

Pidsley, Ruth ;

Deloukas, Panos ;

Frayling, Timothy M. ;

Hattersley, Andrew T. ;

McCarthy, Mark I. ;

Beck, Stephan ;

Hitman, Graham A. .

PLOS ONE, 2010, 5 (11)

[6] Genome-wide DNA methylation profiling using Infinium® assay [J].

Bibikova, Marina ;

Le, Jennie ;

Barnes, Bret ;

Saedinia-Melnyk, Shadi ;

Zhou, Lixin ;

Shen, Richard ;

Gunderson, Kevin L. .

EPIGENOMICS, 2009, 1 (01) :177-200

[7] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].

Birney, Ewan ;

Stamatoyannopoulos, John A. ;

Dutta, Anindya ;

Guigo, Roderic ;

Gingeras, Thomas R. ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Snyder, Michael ;

Dermitzakis, Emmanouil T. ;

Stamatoyannopoulos, John A. ;

Thurman, Robert E. ;

Kuehn, Michael S. ;

Taylor, Christopher M. ;

Neph, Shane ;

Koch, Christoph M. ;

Asthana, Saurabh ;

Malhotra, Ankit ;

Adzhubei, Ivan ;

Greenbaum, Jason A. ;

Andrews, Robert M. ;

Flicek, Paul ;

Boyle, Patrick J. ;

Cao, Hua ;

Carter, Nigel P. ;

Clelland, Gayle K. ;

Davis, Sean ;

Day, Nathan ;

Dhami, Pawandeep ;

Dillon, Shane C. ;

Dorschner, Michael O. ;

Fiegler, Heike ;

Giresi, Paul G. ;

Goldy, Jeff ;

Hawrylycz, Michael ;

Haydock, Andrew ;

Humbert, Richard ;

James, Keith D. ;

Johnson, Brett E. ;

Johnson, Ericka M. ;

Frum, Tristan T. ;

Rosenzweig, Elizabeth R. ;

Karnani, Neerja ;

Lee, Kirsten ;

Lefebvre, Gregory C. ;

Navas, Patrick A. ;

Neri, Fidencio ;

Parker, Stephen C. J. ;

Sabo, Peter J. ;

Sandstrom, Richard ;

Shafer, Anthony .

NATURE, 2007, 447 (7146) :799-816

[8] A transcription factor regulatory circuit in differentiated pancreatic cells [J].

Boj, SF ;

Párrizas, M ;

Maestro, MA ;

Ferrer, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (25) :14481-14486

[9] THE RESPONSE TO LONG-TERM OVERFEEDING IN IDENTICAL-TWINS [J].

BOUCHARD, C ;

TREMBLAY, A ;

DESPRES, JP ;

NADEAU, A ;

LUPIEN, PJ ;

THERIAULT, G ;

DUSSAULT, J ;

MOORJANI, S ;

PINAULT, S ;

FOURNIER, G .

NEW ENGLAND JOURNAL OF MEDICINE, 1990, 322 (21) :1477-1482

[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

← 1 2 3 4 5 6 7 8 →