| Obesity is a complex disease characterized by both environmental and genetic influences. Two different genetic approaches, positional cloning and candidate gene analysis, were used in this study in an attempt to discover genes contributing to obesity.;For the majority of the research presented in this study, individuals from the IRAS Family Study were used. This study consisted of 1425 Hispanic individuals from 90 extended pedigrees and 630 African Americans from 41 extended pedigrees. Genome scan analyses were performed on all individuals to identify regions linked to obesity phenotypes. Several interesting regions were identified, including chromosome 3p26 (African Americans only), 12q13-21 (Hispanics only), and 17q25 (Hispanics only). Fine mapping analysis was performed on all three regions, with chromosome 17q25 remaining the most significant region. Two genes, PPARG and ghrelin, in the chromosomal 3 region were chosen for further analyses, although neither gene indicated a consistent trend of association with obesity. Three genes, SSTR2, GALR2, and GRB2, on chromosome 17 were chosen for association analysis with the linked obesity traits. However, none of the genes showed significant association with the linked traits, although GRB2 displayed consistent evidence of association with VSR. Additionally, SSTR2, although not associated with obesity, was identified to be significantly associated with several glucose homeostasis phenotypes.;For the second genetic approach, several genes were chosen based on their biological function for association analyses with obesity phenotypes. Adiponectin was consistently associated with several obesity traits in the Hispanic population. The most consistent polymorphism was the INS CA repeat at -11156 in the promoter, which was associated with 5 of the 6 measured phenotypes in both single SNP and haplotype analysis.;Proopiomelanocortin (POMC) was also evaluated for association, with several polymorphisms indicating modest yet significant evidence of association with obesity in the Hispanic population. Results are consistent with both single SNP and haplotype analyses.;Another group of obesity candidate genes studied included the melanocortin receptors 2--5. Several SNPs in each gene were evaluated for association with obesity and glucose homeostasis phenotypes. MC5R was the most associated gene with obesity, with all SNPs showing association with waist: hip ratio. MC3R was consistently associated with several glucose homeostasis phenotypes.;In conclusion, several genes and chromosomal regions were tested for association with various measures of obesity. Several interesting findings were discovered, with several genes identified to be significantly associated with obesity. |
