Association analysis of 29,956 individuals confirms that a low- frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion

Diabetes

Volumn 64, Issue 6, 2015, Pages 2279-2285

  Yaghootkar, Hanieh ^a   Stancáková, Alena ^b   Freathy, Rachel M ^a   Vangipurapu, Jagadish ^b   Weedon, Michael N ^a   Xie, Weijia ^a   Wood, Andrew R ^a   Ferrannini, Ele ^c   Mari, Andrea ^d   Ring, Susan M ^e   Lawlor, Debbie A ^e   Smith, George Davey ^e   Jørgensen, Torben ^f,g   Hansen, Torben ^h,i   Pedersen, Oluf ^h   Steinthorsdottir, Valgerdur ^j   Guobjartsson, Daniel F ^j,k   Thorleifsson, Gudmar ^j   Thorsteinsdottir, Unnur ^j,k   Stefansson, Kari ^j,k   Hattersley, Andrew T ^a   Walker, Mark ^l   Morris, Andrew D ^m   Mccarthy, Mark I ^n,o,p   Palmer, Colin N A ^m   Laakso, Markku ^b,q   Frayling, Timothy M ^a   more..

^a UNIVERSITY OF EXETER MEDICAL SCHOOL   (United Kingdom)

^b UNIVERSITY OF EASTERN FINLAND   (Finland)

^c INSTITUTE OF CLINICAL PHYSIOLOGY   (Italy)

^d CNR   (Italy)

^e UNIVERSITY OF BRISTOL   (United Kingdom)

^f GLOSTRUP UNIVERSITY HOSPITAL   (Denmark)

^g UNIVERSITY OF COPENHAGEN   (Denmark)

^h Capital Region   (Denmark)

ⁱ UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^j DECODE GENETICS   (Iceland)

^k UNIVERSITY OF ICELAND   (Iceland)

^l NEWCASTLE UNIVERSITY   (United Kingdom)

^m UNIVERSITY OF DUNDEE   (United Kingdom)

ⁿ UNIVERSITY OF OXFORD   (United Kingdom)

^o UNIVERSITY OF OXFORD   (United Kingdom)

^p NIHR OXFORD BIOMEDICAL RESEARCH CENTRE   (United Kingdom)

^q KUOPIO UNIVERSITY HOSPITAL   (Finland)

more..

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN; PROINSULIN; CCND2 PROTEIN, HUMAN; CYCLIN D2;

ARTICLE; CCND2 GENE; EFFECT SIZE; GENE; GENE FREQUENCY; GENETIC ASSOCIATION STUDY; GENETIC PREDISPOSITION; GENETIC RISK; GENETIC VARIATION; GENOTYPING TECHNIQUE; HUMAN; INSULIN RELEASE; INSULIN SENSITIVITY; MAJOR CLINICAL STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; RISK ASSESSMENT; ALLELE; BODY MASS; GENETICS; GENOTYPE; METABOLISM; SECRETION (PROCESS);

ALLELES; BODY MASS INDEX; CYCLIN D2; DIABETES MELLITUS, TYPE 2; GENE FREQUENCY; GENOTYPE; HUMANS; INSULIN;

EID: 84964697760     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db14-1456     Document Type: Article

References (13)

1. Steinthorsdottir V, Thorleifsson G, Sulem P, et al. Identification of lowfrequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. Nat Genet 2014;46:294-298.
2. Strawbridge RJ, Dupuis J, Prokopenko I, et al.; DIAGRAM Consortium; GIANT Consortium; MuTHER Consortium; CARDIoGRAM Consortium; C4D Consortium. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes 2011;60:2624-2634.
3. Frayling TM, Hattersley AT. Physiology helps GWAS take a step closer to mechanism. Diabetes 2014;63:1836-1837.
4. Stolerman ES, Manning AK, McAteer JB, et al. TCF7L2 variants are associated with increased proinsulin/insulin ratios but not obesity traits in the Framingham Heart Study. Diabetologia 2009;52:614-620.
5. Stancáková A, Javorský M, Kuulasmaa T, Haffner SM, Kuusisto J, Laakso M. Changes in insulin sensitivity and insulin release in relation to glycemia and glucose tolerance in 6, 414 Finnish men. Diabetes 2009;58:1212-1221.
6. Boyd A, Golding J, Macleod J, et al. Cohort Profile: The 'children of the 90s'- The index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol 2013;42:111-127.
7. University of Bristol. Avon Longitudinal Study of Parents and Children [Internet], 2015. Available from http://www.bris.ac.uk/alspac/researchers/dataaccess/data-dictionary/.
8. Jørgensen T, Borch-Johnsen K, Thomsen TF, Ibsen H, Glumer C, Pisinger C. A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur J Cardiovasc Prev Rehabil 2003;10: 377-386.
9. Viechtbauer W. Conducting meta- Analyses in R with the metafor package. J Stat Softw 2010;36:1-48.
10. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta- Analysis. Stat Med 2002;21:1539-1558.
11. Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7- like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 2006;38:320-323.
12. Doney AS, Fischer B, Leese G, Morris AD, Palmer CN. Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG locus: A Go-DARTS study. Arterioscler Thromb Vasc Biol 2004;24:2403-2407.
13. Hills SA, Balkau B, Coppack SW, et al.; EGIR-RISC Study Group. The EGIRRISC STUDY (The European Group for the Study of Insulin Resistance: Relationship between Insulin Sensitivity and Cardiovascular disease risk): I. Methodology and objectives. Diabetologia 2004;47:566-570.