Submitted to: International Journal of Obesity
Publication Type: Peer reviewed journal
Publication Acceptance Date: 2/3/2008
Publication Date: 3/4/2008
Citation: Cai, G., Cole, S.A., Butte, N.F., Voruganti, V.S., Comuzzie, A.G. 2008. Genome-wide scan revealed genetic loci for energy metabolism in Hispanic children and adolescents. International Journal of Obesity. 32:579-585. Interpretive Summary: The genetic contribution to childhood obesity is well recognized; however, the genes regulating body weight in children are yet to be identified. In this study, CNRC researchers sought to identify chromosomal regions that influence energy metabolism in Hispanic children. Our lab characterized and genotyped 1,030 Hispanic children from the Viva La Familia Study, which was designed to investigate genetic and environmental risk factors for the development of obesity in Hispanic families. Our lab measured energy expenditure and fuel utilization over a 24-h period through a whole room calorimeter. We found that certain chromosomal regions harbor genes influencing energy expenditure and fuel utilization in children. Our results show that chromosomal regions on 1, 9, 17, and 18 have genes affecting energy expenditure and substrate oxidation in Hispanic children. Future studies will fine map these chromosomal regions to identify the specific genes.
Technical Abstract: Genome-wide scans were conducted in a search for genetic locations linked to energy expenditure and substrate oxidation in children. Pedigreed data of 1030 Hispanic children and adolescents were from the Viva La Familia Study, which was designed to investigate genetic and environmental risk factors for the development of obesity in Hispanic families. A respiratory calorimeter was used to measure 24-h total energy expenditure (TEE), basal metabolic rate (BMR), sleep metabolic rate (SMR), 24-h respiratory quotient (24RQ), basal metabolic respiratory quotient (BMRQ), and sleep respiratory quotient (SRQ). Protein, fat, and carbohydrate oxidation (PROOX, FATOX, and CHOOX, respectively) were also estimated. All participants were genotyped for 384 single tandem repeat markers spaced an average of 10 cM apart. Computer program SOLAR was used to perform the genetic linkage analyses. Significant linkage for TEE was detected on chromosome 1 near marker D1S2841, with a logarithm of the odds (LOD) score of 4.0. SMR, BMRQ, and PROOX were associated with loci on chromosome 18, 17, and 9, respectively, with LOD scores of 4.88, 3.17, and 4.55, respectively. A genome-wide scan of SMR per kg fat-free mass (SpFFM) peaked in the same region as SMR on chromosome 18 (LOD, 5.24). Suggestive linkage was observed for CHOOX and FATOX. Several candidate genes were found in the above chromosomal regions, including leptin receptor (LEPR). Regions on chromosomes 1, 9, 17, and 18 harbor genes affecting variation in energy expenditure and substrate oxidation in Hispanic children and adolescents.