Genome-wide association study for type 2 diabetes: clinical applications

被引：27

作者：

Lyssenko, Valeriya ^{[1
]}

Groop, Leif

机构：

[1] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, CRC, S-20502 Malmo, Sweden

来源：

CURRENT OPINION IN LIPIDOLOGY | 2009年 / 20卷 / 02期

关键词：

beta-cell function; genome-wide association study; prediction; type; 2; diabetes; TRANSCRIPTION-FACTOR-7-LIKE-2; TCF7L2; GENE; SUSCEPTIBILITY LOCI; INSULIN-SECRETION; BREAST-CANCER; COMPLEX DISEASES; COMMON VARIANTS; ALPHA-GENE; RISK LOCI; POLYMORPHISMS; MELLITUS;

D O I：

10.1097/MOL.0b013e32832923af

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：

Purpose of review Dissecting the genetics of complex polygenic diseases in which environmental factors interact with genetic variants in the predisposition to the disease has not been a trivial task and success has been limited. The purpose of this review is to provide insights into recent advances in genetics of type 2 diabetes. Recent findings In the past year, together the consortia of several genome-wide association studies for type 2 diabetes have identified 19 common variants increasing susceptibility to disease. Most novel loci seem to influence the capacity of beta-cells to increase insulin secretion in response to increase in insulin resistance or body weight. Combined genetic information ultimately might aid in personalized prediction of disease risk; however, genetic tests cannot be offered yet to predict disease. The main reason is that the increased risk associated with each risk variant is small. We have only begun to explore the role of rare variants with stronger effects or copy number variations in the pathogenesis of type 2 diabetes. Summary Rapid progress in the genetics of type 2 diabetes has significantly improved our understanding of disease pathogenesis and provided promising opportunities for drug discoveries over the coming years.

引用

页码：87 / 91

页数：5

共 40 条

[1] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[2] 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

[3] Post Genome-Wide Association Studies of Novel Genes Associated with Type 2 Diabetes Show Gene-Gene Interaction and High Predictive Value [J].

Cauchi, Stephane ;

Meyre, David ;

Durand, Emmanuelle ;

Proenca, Christine ;

Marre, Michel ;

Hadjadj, Samy ;

Choquet, Helene ;

De Graeve, Franck ;

Gaget, Stefan ;

Allegaert, Frederic ;

Delplanque, Jerome ;

Permutt, Marshall Alan ;

Wasson, Jon ;

Blech, Ilana ;

Charpentier, Guillaume ;

Balkau, Beverley ;

Vergnaud, Anne-Claire ;

Czernichow, Sebastien ;

Patsch, Wolfgang ;

Chikri, Mohamed ;

Glaser, Benjamin ;

Sladek, Robert ;

Froguel, Philippe .

PLOS ONE, 2008, 3 (05)

[4] Multiple rare Alleles contribute to low plasma levels of HDL cholesterol [J].

Cohen, JC ;

Kiss, RS ;

Pertsemlidis, A ;

Marcel, YL ;

McPherson, R ;

Hobbs, HH .

SCIENCE, 2004, 305 (5685) :869-872

[5] Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish -: Replication and evidence for a role in both insulin secretion and insulin resistance [J].

Damcott, Coleen M. ;

Pollin, Toni I. ;

Reinhart, Laurie J. ;

Ott, Sandra H. ;

Shen, Haiqing ;

Silver, Kristi D. ;

Mitchell, Braxton D. ;

Shuldiner, Alan R. .

DIABETES, 2006, 55 (09) :2654-2659

[6] Genome-wide association study identifies novel breast cancer susceptibility loci [J].

Easton, Douglas F. ;

Pooley, Karen A. ;

Dunning, Alison M. ;

Pharoah, Paul D. P. ;

Thompson, Deborah ;

Ballinger, Dennis G. ;

Struewing, Jeffery P. ;

Morrison, Jonathan ;

Field, Helen ;

Luben, Robert ;

Wareham, Nicholas ;

Ahmed, Shahana ;

Healey, Catherine S. ;

Bowman, Richard ;

Meyer, Kerstin B. ;

Haiman, Christopher A. ;

Kolonel, Laurence K. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Brennan, Paul ;

Sangrajrang, Suleeporn ;

Gaborieau, Valerie ;

Odefrey, Fabrice ;

Shen, Chen-Yang ;

Wu, Pei-Ei ;

Wang, Hui-Chun ;

Eccles, Diana ;

Evans, D. Gareth ;

Peto, Julian ;

Fletcher, Olivia ;

Johnson, Nichola ;

Seal, Sheila ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Chenevix-Trench, Georgia ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Nevanlinna, Heli ;

Fagerholm, Rainer ;

Eerola, Hannaleena ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong-Young ;

Ahn, Sei-Hyun .

NATURE, 2007, 447 (7148) :1087-U7

[7] TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program [J].

Florez, Jose C. ;

Jablonski, Kathleen A. ;

Bayley, Nick ;

Pollin, Toni I. ;

de Bakker, Paul I. W. ;

Shuldiner, Alan R. ;

Knowler, William C. ;

Nathan, David M. ;

Altshuler, David .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (03) :241-250

[8] Metabolic consequences of a family history of NIDDM (The Botnia Study) - Evidence for sex-specific parental effects [J].

Groop, L ;

Forsblom, C ;

Lehtovirta, M ;

Tuomi, T ;

Karanko, S ;

Nissen, M ;

Ehrnstrom, BO ;

Forsen, B ;

Isomaa, B ;

Snickars, B ;

Taskinen, MR .

DIABETES, 1996, 45 (11) :1585-1593

[9] The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm [J].

Helgadottir, Anna ;

Thorleifsson, Gudmar ;

Magnusson, Kristinn P. ;

Gretarsdottir, Solveig ;

Steinthorsdottir, Valgerdur ;

Manolescu, Andrei ;

Jones, Gregory T. ;

Rinkel, Gabriel J. E. ;

Blankensteijn, Jan D. ;

Ronkainen, Antti ;

Jaaskelainen, Juha E. ;

Kyo, Yoshiki ;

Lenk, Guy M. ;

Sakalihasan, Natzi ;

Kostulas, Konstantinos ;

Gottsater, Anders ;

Flex, Andrea ;

Stefansson, Hreinn ;

Hansen, Torben ;

Andersen, Gitte ;

Weinsheimer, Shantel ;

Borch-Johnsen, Knut ;

Jorgensen, Torben ;

Shah, Svati H. ;

Quyyumi, Arshed A. ;

Granger, Christopher B. ;

Reilly, Muredach P. ;

Austin, Harland ;

Levey, Allan I. ;

Vaccarino, Viola ;

Palsdottir, Ebba ;

Walters, G. Bragi ;

Jonsdottir, Thorbjorg ;

Snorradottir, Steinunn ;

Magnusdottir, Dana ;

Gudmundsson, Gudmundur ;

Ferrell, Robert E. ;

Sveinbjornsdottir, Sigurlaug ;

Hernesniemi, Juha ;

Niemela, Mika ;

Limet, Raymond ;

Andersen, Karl ;

Sigurdsson, Gunnar ;

Benediktsson, Rafn ;

Verhoeven, Eric L. G. ;

Teijink, Joep A. W. ;

Grobbee, Diederick E. ;

Rader, Daniel J. ;

Collier, David A. ;

Pedersen, Oluf .

NATURE GENETICS, 2008, 40 (02) :217-224

[10] A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer [J].

Hunter, David J. ;

Kraft, Peter ;

Jacobs, Kevin B. ;

Cox, David G. ;

Yeager, Meredith ;

Hankinson, Susan E. ;

Wacholder, Sholom ;

Wang, Zhaoming ;

Welch, Robert ;

Hutchinson, Amy ;

Wang, Junwen ;

Yu, Kai ;

Chatterjee, Nilanjan ;

Orr, Nick ;

Willett, Walter C. ;

Colditz, Graham A. ;

Ziegler, Regina G. ;

Berg, Christine D. ;

Buys, Saundra S. ;

McCarty, Catherine A. ;

Feigelson, Heather Spencer ;

Calle, Eugenia E. ;

Thun, Michael J. ;

Hayes, Richard B. ;

Tucker, Margaret ;

Gerhard, Daniela S. ;

Fraumeni, Joseph F., Jr. ;

Hoover, Robert N. ;

Thomas, Gilles ;

Chanock, Stephen J. .

NATURE GENETICS, 2007, 39 (07) :870-874

← 1 2 3 4 →

共 40 条

[1] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[2] 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

[3] Post Genome-Wide Association Studies of Novel Genes Associated with Type 2 Diabetes Show Gene-Gene Interaction and High Predictive Value [J].

Cauchi, Stephane ;

Meyre, David ;

Durand, Emmanuelle ;

Proenca, Christine ;

Marre, Michel ;

Hadjadj, Samy ;

Choquet, Helene ;

De Graeve, Franck ;

Gaget, Stefan ;

Allegaert, Frederic ;

Delplanque, Jerome ;

Permutt, Marshall Alan ;

Wasson, Jon ;

Blech, Ilana ;

Charpentier, Guillaume ;

Balkau, Beverley ;

Vergnaud, Anne-Claire ;

Czernichow, Sebastien ;

Patsch, Wolfgang ;

Chikri, Mohamed ;

Glaser, Benjamin ;

Sladek, Robert ;

Froguel, Philippe .

PLOS ONE, 2008, 3 (05)

[4] Multiple rare Alleles contribute to low plasma levels of HDL cholesterol [J].

Cohen, JC ;

Kiss, RS ;

Pertsemlidis, A ;

Marcel, YL ;

McPherson, R ;

Hobbs, HH .

SCIENCE, 2004, 305 (5685) :869-872

Damcott, Coleen M. ;

Pollin, Toni I. ;

Reinhart, Laurie J. ;

Ott, Sandra H. ;

Shen, Haiqing ;

Silver, Kristi D. ;

Mitchell, Braxton D. ;

Shuldiner, Alan R. .

DIABETES, 2006, 55 (09) :2654-2659

[6] Genome-wide association study identifies novel breast cancer susceptibility loci [J].

Easton, Douglas F. ;

Pooley, Karen A. ;

Dunning, Alison M. ;

Pharoah, Paul D. P. ;

Thompson, Deborah ;

Ballinger, Dennis G. ;

Struewing, Jeffery P. ;

Morrison, Jonathan ;

Field, Helen ;

Luben, Robert ;

Wareham, Nicholas ;

Ahmed, Shahana ;

Healey, Catherine S. ;

Bowman, Richard ;

Meyer, Kerstin B. ;

Haiman, Christopher A. ;

Kolonel, Laurence K. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Brennan, Paul ;

Sangrajrang, Suleeporn ;

Gaborieau, Valerie ;

Odefrey, Fabrice ;

Shen, Chen-Yang ;

Wu, Pei-Ei ;

Wang, Hui-Chun ;

Eccles, Diana ;

Evans, D. Gareth ;

Peto, Julian ;

Fletcher, Olivia ;

Johnson, Nichola ;

Seal, Sheila ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Chenevix-Trench, Georgia ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Nevanlinna, Heli ;

Fagerholm, Rainer ;

Eerola, Hannaleena ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong-Young ;

Ahn, Sei-Hyun .

NATURE, 2007, 447 (7148) :1087-U7

[7] TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program [J].

Florez, Jose C. ;

Jablonski, Kathleen A. ;

Bayley, Nick ;

Pollin, Toni I. ;

de Bakker, Paul I. W. ;

Shuldiner, Alan R. ;

Knowler, William C. ;

Nathan, David M. ;

Altshuler, David .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (03) :241-250

[8] Metabolic consequences of a family history of NIDDM (The Botnia Study) - Evidence for sex-specific parental effects [J].

Groop, L ;

Forsblom, C ;

Lehtovirta, M ;

Tuomi, T ;

Karanko, S ;

Nissen, M ;

Ehrnstrom, BO ;

Forsen, B ;

Isomaa, B ;

Snickars, B ;

Taskinen, MR .

DIABETES, 1996, 45 (11) :1585-1593

[9] The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm [J].

Helgadottir, Anna ;

Thorleifsson, Gudmar ;

Magnusson, Kristinn P. ;

Gretarsdottir, Solveig ;

Steinthorsdottir, Valgerdur ;

Manolescu, Andrei ;

Jones, Gregory T. ;

Rinkel, Gabriel J. E. ;

Blankensteijn, Jan D. ;

Ronkainen, Antti ;

Jaaskelainen, Juha E. ;

Kyo, Yoshiki ;

Lenk, Guy M. ;

Sakalihasan, Natzi ;

Kostulas, Konstantinos ;

Gottsater, Anders ;

Flex, Andrea ;

Stefansson, Hreinn ;

Hansen, Torben ;

Andersen, Gitte ;

Weinsheimer, Shantel ;

Borch-Johnsen, Knut ;

Jorgensen, Torben ;

Shah, Svati H. ;

Quyyumi, Arshed A. ;

Granger, Christopher B. ;

Reilly, Muredach P. ;

Austin, Harland ;

Levey, Allan I. ;

Vaccarino, Viola ;

Palsdottir, Ebba ;

Walters, G. Bragi ;

Jonsdottir, Thorbjorg ;

Snorradottir, Steinunn ;

Magnusdottir, Dana ;

Gudmundsson, Gudmundur ;

Ferrell, Robert E. ;

Sveinbjornsdottir, Sigurlaug ;

Hernesniemi, Juha ;

Niemela, Mika ;

Limet, Raymond ;

Andersen, Karl ;

Sigurdsson, Gunnar ;

Benediktsson, Rafn ;

Verhoeven, Eric L. G. ;

Teijink, Joep A. W. ;

Grobbee, Diederick E. ;

Rader, Daniel J. ;

Collier, David A. ;

Pedersen, Oluf .

NATURE GENETICS, 2008, 40 (02) :217-224

[10] A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer [J].

Hunter, David J. ;

Kraft, Peter ;

Jacobs, Kevin B. ;

Cox, David G. ;

Yeager, Meredith ;

Hankinson, Susan E. ;

Wacholder, Sholom ;

Wang, Zhaoming ;

Welch, Robert ;

Hutchinson, Amy ;

Wang, Junwen ;

Yu, Kai ;

Chatterjee, Nilanjan ;

Orr, Nick ;

Willett, Walter C. ;

Colditz, Graham A. ;

Ziegler, Regina G. ;

Berg, Christine D. ;

Buys, Saundra S. ;

McCarty, Catherine A. ;

Feigelson, Heather Spencer ;

Calle, Eugenia E. ;

Thun, Michael J. ;

Hayes, Richard B. ;

Tucker, Margaret ;

Gerhard, Daniela S. ;

Fraumeni, Joseph F., Jr. ;

Hoover, Robert N. ;

Thomas, Gilles ;

Chanock, Stephen J. .

NATURE GENETICS, 2007, 39 (07) :870-874

← 1 2 3 4 →