We completed genotyping subjects with the Affymetrix 1 Million SNP chip technology. Phase 1 was designed to detect potential associations with young-onset type 2 diabetes, by genotyping 300 early-onset type 2 diabetes subjects (onset age<25 yrs) and 329 non-diabetic controls (age >45 yrs), and 271 additional subjects who were diabetic and non-diabetic siblings of the selected subjects. Associations with diabetes were calculated using both a case/control analysis (N= 629) and a within-family analysis (482 siblings from 169 sibships), and SNPs that had the strongest association for the combined associations were prioritized. Phase 2 of the GWA was designed to detect associations with pre-diabetic traits (% body fat, insulin action as measured by the hyperinsulinemic euglycemic clamp technique, and the acute insulin response to an intravenous bolus of glucose). Six hundred non-diabetic subjects who had been metabolically phenotyped for these predictors of diabetes were genotyped using the 1 Million SNP chip. SNPs that provided the best associations for diabetes and/or a pre-diabetic trait were selected for additional genotyping in a population-based sample of 3501 full-heritage Pima Indians. This genotyping utilized a new high throughput technology (Bead Express). We recently completed genotyping the best signals from our genome-wide association analysis in the sample of 3501 full hertiage Pima Indians and are currently replicating the best SNPs from this sample in a second population-based sample of 3784 mixed heritage Native Americans. To date the strongest replications for BMI were with SNPs in HLA-DOA, HEATR5B and an intergenic region near NOVA1 (for each SNP the combined sample P for BMI = 8 x 10-7, 5 x 10-7, and 1 x 10-6, respectively).
| Traurig, Michael T; Orczewska, Julieanna I; Ortiz, Daniel J et al. (2013) Evidence for a role of LPGAT1 in influencing BMI and percent body fat in Native Americans. Obesity (Silver Spring) 21:193-202 |
| Hanson, Robert L; Guo, Tingwei; Muller, Yunhua L et al. (2013) Strong Parent-of-Origin Effects in the Association of KCNQ1 Variants With Type 2 Diabetes in American Indians. Diabetes 62:2984-91 |
| Bian, Li; Traurig, Michael; Hanson, Robert L et al. (2013) MAP2K3 is associated with body mass index in American Indians and Caucasians and may mediate hypothalamic inflammation. Hum Mol Genet : |
| Malhotra, Alka; Kobes, Sayuko; Knowler, William C et al. (2011) A genome-wide association study of BMI in American Indians. Obesity (Silver Spring) 19:2102-6 |
| Ma, Lijun; Hanson, Robert L; Traurig, Michael T et al. (2010) Evaluation of A2BP1 as an obesity gene. Diabetes 59:2837-45 |
