Insights into the Genetic Susceptibility to Type 2 Diabetes from Genome-Wide Association Studies of Glycaemic Traits

被引：34

作者：

Marullo, Letizia ^{[1
]}

Moustafa, Julia S. El-Sayed ^{[2
]}

Prokopenko, Inga ^{[2
]}

机构：

[1] Univ Ferrara, Genet Sect, Dept Life Sci & Biotechnol, I-44121 Ferrara, Italy

[2] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, Hammersmith Hosp, London W12 0NN, England

来源：

CURRENT DIABETES REPORTS | 2014年 / 14卷 / 11期

关键词：

2-h post-prandial glucose; Association; beta-cell function; Birth weight; Body mass index; Candidate gene study; Cardiometabolic traits; Effect size; Fasting glucose; Fasting insulin; Genome-wide association study; Glycated haemoglobin (HbA(1c)); Homeostasis model assessment of beta-cell function (HOMA-B); Homeostasis model assessment of insulin resistance (HOMA-IR); Insulin resistance; Insulin secretion; Maturity-onset diabetes of the young (MODY); Meta-analysis; Oral glucose tolerance test (OGTT); Proinsulin; Risk prediction; Single nucleotide polymorphism (SNP); Thrifty gene hypothesis; Type; 2; diabetes; FASTING PLASMA-GLUCOSE; HOMEOSTASIS MODEL ASSESSMENT; INSULIN-RESISTANCE; BIRTH-WEIGHT; RISK-FACTORS; THRIFTY GENOTYPE; COMMON VARIANTS; FOLLOW-UP; LOCI; GLUCOKINASE;

D O I：

10.1007/s11892-014-0551-8

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Over the past 8 years, the genetics of complex traits have benefited from an unprecedented advancement in the identification of common variant loci for diseases such as type 2 diabetes (T2D). The ability to undertake genome-wide association studies in large population-based samples for quantitative glycaemic traits has permitted us to explore the hypothesis that models arising from studies in non-diabetic individuals may reflect mechanisms involved in the pathogenesis of diabetes. Amongst 88 T2D risk and 72 glycaemic trait loci, only 29 are shared and show disproportionate magnitudes of phenotypic effects. Important mechanistic insights have been gained regarding the physiological role of T2D loci in disease predisposition through the elucidation of their contribution to glycaemic trait variability. Further investigation is warranted to define causal variants within these loci, including functional characterisation of associated variants, to dissect their role in disease mechanisms and to enable clinical translation.

引用

页码：1 / 17

页数：17

共 98 条

[1] Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes [J].

Albrechtsen, A. ;

Grarup, N. ;

Li, Y. ;

Sparso, T. ;

Tian, G. ;

Cao, H. ;

Jiang, T. ;

Kim, S. Y. ;

Korneliussen, T. ;

Li, Q. ;

Nie, C. ;

Wu, R. ;

Skotte, L. ;

Morris, A. P. ;

Ladenvall, C. ;

Cauchi, S. ;

Stancakova, A. ;

Andersen, G. ;

Astrup, A. ;

Banasik, K. ;

Bennett, A. J. ;

Bolund, L. ;

Charpentier, G. ;

Chen, Y. ;

Dekker, J. M. ;

Doney, A. S. F. ;

Dorkhan, M. ;

Forsen, T. ;

Frayling, T. M. ;

Groves, C. J. ;

Gui, Y. ;

Hallmans, G. ;

Hattersley, A. T. ;

He, K. ;

Hitman, G. A. ;

Holmkvist, J. ;

Huang, S. ;

Jiang, H. ;

Jin, X. ;

Justesen, J. M. ;

Kristiansen, K. ;

Kuusisto, J. ;

Lajer, M. ;

Lantieri, O. ;

Li, W. ;

Liang, H. ;

Liao, Q. ;

Liu, X. ;

Ma, T. ;

Ma, X. .

DIABETOLOGIA, 2013, 56 (02) :298-310

[2] A haplotype map of the human genome [J].

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 .

NATURE, 2005, 437 (7063) :1299-1320

[3]

Amer Diabet Assoc, 2011, DIABETES CARE, V34, pS11, DOI [10.2337/dc10-S062, 10.2337/dc14-S081, 10.2337/dc11-S011, 10.2337/dc13-S011, 10.2337/dc13-S067, 10.2337/dc12-s064, 10.2337/dc11-S062, 10.2337/dc10-S011, 10.2337/dc12-s011]

[4] Genome-wide linkage scans for fasting glucose, insulin, and insulin resistance in the National Heart, Lung, and Blood Institute Family Blood Pressure Program - Evidence of linkages to chromosome 7q36 and 19q13 from meta-analysis [J].

An, P ;

Freedman, BI ;

Hanis, CL ;

Chen, YDI ;

Weder, AB ;

Schork, NJ ;

Boerwinkle, E ;

Province, MA ;

Hsiung, CA ;

Wu, XD ;

Quertermous, T ;

Rao, DC .

DIABETES, 2005, 54 (03) :909-914

[5]

[Anonymous], 2013, IDF DIABETES ATLAS

[6]

[Anonymous], 2006, Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia: Report of a WHO/IDF consultation

[7] Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts [J].

Aulchenko, Yurii S. ;

Ripatti, Samuli ;

Lindqvist, Ida ;

Boomsma, Dorret ;

Heid, Iris M. ;

Pramstaller, Peter P. ;

Penninx, Brenda W. J. H. ;

Janssens, A. Cecile J. W. ;

Wilson, James F. ;

Spector, Tim ;

Martin, Nicholas G. ;

Pedersen, Nancy L. ;

Kyvik, Kirsten Ohm ;

Kaprio, Jaakko ;

Hofman, Albert ;

Freimer, Nelson B. ;

Jarvelin, Marjo-Riitta ;

Gyllensten, Ulf ;

Campbell, Harry ;

Rudan, Igor ;

Johansson, Asa ;

Marroni, Fabio ;

Hayward, Caroline ;

Vitart, Veronique ;

Jonasson, Inger ;

Pattaro, Cristian ;

Wright, Alan ;

Hastie, Nick ;

Pichler, Irene ;

Hicks, Andrew A. ;

Falchi, Mario ;

Willemsen, Gonneke ;

Hottenga, Jouke-Jan ;

de Geus, Eco J. C. ;

Montgomery, Grant W. ;

Whitfield, John ;

Magnusson, Patrik ;

Saharinen, Juha ;

Perola, Markus ;

Silander, Kaisa ;

Isaacs, Aaron ;

Sijbrands, Eric J. G. ;

Uitterlinden, Andre G. ;

Witteman, Jacqueline C. M. ;

Oostra, Ben A. ;

Elliott, Paul ;

Ruokonen, Aimo ;

Sabatti, Chiara ;

Gieger, Christian ;

Meitinger, Thomas .

NATURE GENETICS, 2009, 41 (01) :47-55

[8] Revisiting the Thrifty Gene Hypothesis via 65 Loci Associated with Susceptibility to Type 2 Diabetes [J].

Ayub, Qasim ;

Moutsianas, Loukas ;

Chen, Yuan ;

Panoutsopoulou, Kalliope ;

Colonna, Vincenza ;

Pagani, Luca ;

Prokopenko, Inga ;

Ritchie, Graham R. S. ;

Tyler-Smith, Chris ;

McCarthy, Mark I. ;

Zeggini, Eleftheria ;

Xue, Yali .

AMERICAN JOURNAL OF HUMAN GENETICS, 2014, 94 (02) :176-185

[9] Predicting Diabetes: Clinical, Biological, and Genetic Approaches Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) [J].

Balkau, Beverley ;

Lange, Celine ;

Fezeu, Leopold ;

Tichet, Jean ;

De Lauzon-Guillain, Blandine ;

Cernichow, Sebastien ;

Fumeron, Frederic ;

Froguel, Philippe ;

Vaxillaire, Martine ;

Cauchi, Stephane ;

Ducimetiere, Pierre ;

Eschwege, Eveline .

DIABETES CARE, 2008, 31 (10) :2056-2061

[10] Insights Into the Pathogenicity of Rare Missense GCK Variants From the Identification and Functional Characterization of Compound Heterozygous and Double Mutations Inherited in Cis [J].

Beer, Nicola L. ;

Osbak, Kara K. ;

van de Bunt, Martun ;

Tribble, Nicholas D. ;

Steele, Anna M. ;

Wensley, Kirsty J. ;

Edghill, Emma L. ;

Colcough, Kevin ;

Barrett, Amy ;

Valentinova, Lucia ;

Rundle, Jana K. ;

Raimondo, Anne ;

Grimsby, Joseph ;

Ellard, Sian ;

Gloyn, Anna L. .

DIABETES CARE, 2012, 35 (07) :1482-1484

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