In the current project, the techniques of classic epidemiology and of genetic epidemiology are being used to identify determinants of type 2 diabetes, its risk factors and its complications. The effects of genetic factors are assessed in other projects (DK069028-24, Genetic Epidemiology of Diabetes and Obesity and DK069094-06, Genetic Epidemiology of Diabetic Complications);the present study focuses on molecular processes that are downstream of genetic factors, such as gene transcription, protein expression and cellular metabolism. Longitudinal studies are being conducted in individuals at high risk for type 2 diabetes in urban Phoenix. Samples are collected that suitable for RNA extraction and for large scale studies of protein levels and metabolomics. Information on family membership is collected for inclusion in family-based analyses. Recent analyses of genome-wide transcription in skeletal muscle tissue have shown that a small number of transcripts have a clearly bimodal frequency distribution;the vast majority of these are accounted for by the effect of a genetic polymorphism in close proximity the region encoding for the transcript. Large scale genome-wide transcription profiles are also being measured in peripheral blood samples in collaboration with investigators from Texas Biomedical Research Institute. Initial analyses have shown a large number of transcripts associated with age and sex, and these data are being compared with those from other cohorts in a collaborative meta-analysis. Analyses of the relationship of transcription in peripheral blood samples with diabetes, obesity and related factors are currently in process, as is the assessment of heritability. Recruitment of additional individuals and families and longitudinal follow-up are also ongoing.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2013
Total Cost
$442,916
Indirect Cost
City
State
Country
Zip Code
Grice, Brian A; Nelson, Robert G; Williams, Desmond E et al. (2017) Associations between persistent organic pollutants, type 2 diabetes, diabetic nephropathy and mortality. Occup Environ Med 74:521-527
Chang, Douglas C; Piaggi, Paolo; Hanson, Robert L et al. (2017) Autoantibodies against PFDN2 are associated with an increased risk of type 2 diabetes: A case-control study. Diabetes Metab Res Rev :
Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang et al. (2017) Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun 8:80
Schick, Ursula M; Jain, Deepti; Hodonsky, Chani J et al. (2016) Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans. Am J Hum Genet 98:229-42
Traurig, Michael; Hanson, Robert L; Marinelarena, Alejandra et al. (2016) Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression. Diabetes 65:510-9
Peters, Marjolein J; Joehanes, Roby; Pilling, Luke C et al. (2015) The transcriptional landscape of age in human peripheral blood. Nat Commun 6:8570
Mason, Clinton C; Hanson, Robert L; Ossowski, Vicky et al. (2011) Bimodal distribution of RNA expression levels in human skeletal muscle tissue. BMC Genomics 12:98