Population Genetics of Type 2 Diabetes

This multi-level inquiry into the complex influences on type 2 diabetes (T2D) susceptibility requires the use of multiple heterogeneous datasets, mining of thousands of text references for patterns of information that may be relevant to T2D research, modeling of relationships found, and presentation of newly developed knowledge in a form that is easy to grasp. Development of NCIBI resources and their integration with statistical genetics methods is improving the efficiency and completeness of work in T2D research and is providing direction and motivation to maximize the effectiveness of the NCIBI resources for all researchers.

Overall Goals

1. To identify genes with genetic variation that increases the risk of type 2 diabetes (T2D).
2. To understand better the biology of T2D and associated quantitative traits.

Specific Aims

1. To employ the NCIBI suite of tools and other bioinformatics resources (Gene Ontology, KEGG, Snipper, Panther) to analyze physical interactions and biological relationships, networks, or pathways involving genes in the T2D-associated regions and look for enrichment of functional categories.
2. To develop statistical models of dealing with over-representation of the large number of interactions for a small number of genes and of quantifying function overlap for the genes from the same associated region in T2D patients.

Related Publications

Black MH, Fingerlin TE, Allayee H, Zhang W, Xiang AH, Trigo E, Hartiala J, Lehtinen AB, Haffner SM, Bergman RN, McEachin RC, Kjos SL, Lawrence JM, Buchanan TA, Watanabe RM. Evidence of interaction between PPARG2 and HNF4A contributing to variation in insulin sensitivity in Mexican Americans. Diabetes 2008; 57(4): 1048-56. PMID: 18162503.

Chen WM, Erdos MR, Jackson AU, Saxena R, Sanna S, Silver KD, Timpson NJ, Hansen T, Orrù M, Grazia Piras M, Bonnycastle LL, Willer CJ, Lyssenko V, Shen H, Kuusisto J, Ebrahim S, Sestu N, Duren WL, Spada MC, Stringham HM, Scott LJ, Olla N, Swift AJ, Najjar S, Mitchell BD, Lawlor DA, Smith GD, Ben-Shlomo Y, Andersen G, Borch-Johnsen K, Jørgensen T, Saramies J, Valle TT, Buchanan TA, Shuldiner AR, Lakatta E, Bergman RN, Uda M, Tuomilehto J, Pedersen O, Cao A, Groop L, Mohlke KL, Laakso M, Schlessinger D, Collins FS, Altshuler D, Abecasis GR, Boehnke M, Scuteri A, Watanabe RM. Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. J Clin Invest 2008; 118(7): 2620-8. PMID: 18521185.

Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, Hu T, de Bakker PI, Abecasis GR, Almgren P, Andersen G, Ardlie K, Boström KB, Bergman RN, Bonnycastle LL, Borch-Johnsen K, Burtt NP, Chen H, Chines PS, Daly MJ, Deodhar P, Ding CJ, Doney AS, Duren WL, Elliott KS, Erdos MR, Frayling TM, Freathy RM, Gianniny L, Grallert H, Grarup N, Groves CJ, Guiducci C, Hansen T, Herder C, Hitman GA, Hughes TE, Isomaa B, Jackson AU, Jørgensen T, Kong A, Kubalanza K, Kuruvilla FG, Kuusisto J, Langenberg C, Lango H, Lauritzen T, Li Y, Lindgren CM, Lyssenko V, Marvelle AF, Meisinger C, Midthjell K, Mohlke KL, Morken MA, Morris AD, Narisu N, Nilsson P, Owen KR, Palmer CN, Payne F, Perry JR, Pettersen E, Platou C, Prokopenko I, Qi L, Qin L, Rayner NW, Rees M, Roix JJ, Sandbaek A, Shields B, Sjögren M, Steinthorsdottir V, Stringham HM, Swift AJ, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tuomi T, Tuomilehto J, Walker M, Watanabe RM, Weedon MN, Willer CJ, Wellcome Trust Case Control Consortium, Illig T, Hveem K, Hu FB, Laakso M, Stefansson K, Pedersen O, Wareham NJ, Barroso I, Hattersley AT, Collins FS, Groop L, McCarthy MI, Boehnke M, Altshuler D. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 2008; 40(5): 638-45. PMID: 18372903.

Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 2007; 316(5829): 1341-5. PMID: 17463248.

Scott LJ, Bonnycastle LL, Willer CJ, Sprau AG, Jackson AU, Narisu N, Duren WL, Chines PS, Stringham HM, Erdos MR, Valle TT, Tuomilehto J, Bergman RN, Mohlke KL, Collins FS, Boehnke M. Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Diabetes 2006; 55(9): 2649-53. PMID: 16936217.

Mohlke KL, Jackson AU, Scott LJ, Peck EC, Suh YD, Chines PS, Watanabe RM, Buchanan TA, Conneely KN, Erdos MR, Narisu N, Enloe S, Valle TT, Tuomilehto J, Bergman RN, Boehnke M, Collins FS. Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns. Hum Genet 2005; 118(2): 245-54. PMID: 16142453.