Linkage of Type 2 Diabetes on Chromosome 9p24 in Mexican Americans: Additional Evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

• Published in: Human heredity 2013-01, Vol.76 (1), p.36-46
• Main Authors: Farook, Vidya S., Coletta, Dawn K., Puppala, Sobha, Schneider, Jennifer, Chittoor, Geetha, Hu, Shirley L., Winnier, Deidre A., Norton, Luke, Dyer, Thomas D., Arya, Rector, Cole, Shelley A., Carless, Melanie, Göring, Harald H., Almasy, Laura, Mahaney, Michael C., Comuzzie, Anthony G., Curran, Joanne E., Blangero, John, Duggirala, Ravindranath, Lehman, Donna M., Jenkinson, Christopher P., DeFronzo, Ralph A.
• Format: Article
• Language: English
• Subjects: Adult; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 9; Diabetes; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Female; Genetic Linkage; Genetic Predisposition to Disease; Genome-Wide Association Study; Hispanic Americans; Humans; Male; Mexican Americans - genetics; Middle Aged; Original Paper; Population genetics
• ISSN: 0001-5652; 1423-0062
• DOI: 10.1159/000354849

Objective: Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage (GWL) analysis to localize T2DM susceptibility loci in Mexican Americans. Methods: We used the phenotypic and genotypic data from 1,122 Mexican-American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). GWL analysis was performed using the variance components approach. Data from 2 additional Mexican-American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results: After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h 2 = 0.62, p = 2.7 × 10 -6 ). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region also in SAFDGS, we found the significant and increased linkage evidence (LOD = 4.3, empirical p = 1.0 × 10 -5 , genome-wide p = 1.6 × 10 -3 ) for T2DM at the same chromosomal region, when we performed a GWL analysis of the VAGES data combined with the SAFHS and SAFDGS data. Conclusion: Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies involving T2DM-related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes.