Identifying genetic risk for type 2 diabetes and obesity

2014

Challenge

Type 2 diabetes and obesity disproportionally affect minority populations, in particular American Indians, who are more than twice as likely as white Americans to have diabetes external link arrow icon. Identifying genetic variations that increase American Indians’ risk for type 2 diabetes and obesity could help researchers develop better prevention strategies for both this group and among the broader population.

Advance

IRP researchers led by Robert Hanson, M.D., M.P.H., and Leslie J. Baier, Ph.D., identified several genes that affect type 2 diabetes and obesity risk by studying Pima Indians, a group particularly prone to these issues. By applying molecular-genetic approaches to biological samples and examining family histories collected over decades of research with the Pima Indian population, the researchers found that one gene variant, if inherited from the mother, nearly doubles the risk for type 2 diabetes. Another gene variant discovered via this research causes children to become overweight and obese at very young ages.

Impact

Genetic testing for high-risk variants can help identify people who would benefit from early intervention, potentially reducing the prevalence of diabetes and obesity among the Pima Indian population. These studies could also help identify novel therapeutic targets that might lead to improved treatments.

Publications

Hanson RL, Muller YL, Kobes S, Guo T, Bian L, Ossowski V, Wiedrich K, Sutherland J, Wiedrich C, Mahkee D, Huang K, Abdussamad M, Traurig M, Weil EJ, Nelson RG, Bennett PH, Knowler WC, Bogardus C, Baier LJ. (2014). A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes. Diabetes. 63(1), 369-76.

Bian L, Traurig M, Hanson RL, Marinelarena A, Kobes S, Muller YL, Malhotra A, Huang K, Perez J, Gale A, Knowler WC, Bogardus C, Baier LJ. (2013). MAP2K3 is associated with body mass index in American Indians and Caucasians and may mediate hypothalamic inflammation. Hum Mol Genet. 22(21), 4438-49.

Hanson RL, Guo T, Muller YL, Fleming J, Knowler WC, Kobes S, Bogardus C, Baier LJ. (2013). Strong parent-of-origin effects in the association of KCNQ1 variants with type 2 diabetes in American Indians. Diabetes. 62(8), 2984-91.

Thearle MS, Muller YL, Hanson RL, Mullins M, Abdussamad M, Tran J, Knowler WC, Bogardus C, Krakoff J, Baier LJ. (2012). Greater impact of melanocortin-4 receptor deficiency on rates of growth and risk of type 2 diabetes during childhood compared with adulthood in Pima Indians. Diabetes. 61(1), 250-7.

Traurig M, Mack J, Hanson RL, Ghoussaini M, Meyre D, Knowler WC, Kobes S, Froguel P, Bogardus C, Baier LJ. (2009). Common variation in SIM1 is reproducibly associated with BMI in Pima Indians. Diabetes. 58(7), 1682-9.