PEDIATRIC HIGHLIGHT Genome-wide scan revealed genetic loci for energy metabolism in Hispanic children and adolescents G Cai 1 , SA Cole 2 , NF Butte 1 , VS Voruganti 2 and AG Comuzzie 2 1 USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA and 2 Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA Objective: Genome-wide scans were conducted in search for genetic locations linked to energy expenditure and substrate oxidation in children. Design: 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. Results: 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). Conclusion: Regions on chromosomes 1, 9, 17 and 18 harbor genes affecting variation in energy expenditure and substrate oxidation in Hispanic children and adolescents. International Journal of Obesity (2008) 32, 579–585; doi:10.1038/ijo.2008.20; published online 4 March 2008 Keywords: energy expenditure; genome-wide scan; genetic linkage; childhood obesity Introduction Childhood obesity in the United States has increased dramatically in the past two decades, especially among Hispanic children. In 2003–2004, the prevalence of over- weight, defined as X95th body mass index (BMI) percentile, was 19.2% in Mexican-American children. 1 The epidemic of childhood obesity is attributed to an interaction between a genetic predisposition and an environment of readily available food and sedentary lifestyle. Weight gain in adults has been associated with a low resting metabolic rate 2 and a low ratio of fat (FATOX) to carbohydrate oxidation (CHOOX). 3 A familial aggregation was demonstrated for metabolic rate 4 and respiratory quotient (RQ), an indicator of CHOOX to FATOX. 5 Twin studies 6,7 suggested a genetic influence on resting metabolic rate. A linkage study in Pima Indians detected quantitative trait loci (QTLs) on chromo- some 1p31 and 20q11.2 influencing 24-h respiratory quotient (24RQ). 8 The genetic architecture of childhood obesity is incomp- letely understood. Although a few pediatric studies have reported the heritability of fat mass (FM), 9,10 few have investigated the heritability and QTL effect of the mediators of childhood obesity such as metabolic rate and nutrient oxidation. We have reported the heritabilities for body size and composition, diet, physical activity and metabolic risk factors for children and adolescents enrolled in the Viva La Familia Study which was designed to investigate genetic and environmental factors underlying childhood obesity in the Hispanic population. 11 Here, we present genome-wide screening results for energy expendi- ture and substrate utilization for the Viva La Familia Study. Received 25 April 2007; revised 1 February 2008; accepted 3 February 2008; published online 4 March 2008 Correspondence: Dr NF Butte, USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA. E-mail: nbutte@bcm.tmc.edu International Journal of Obesity (2008) 32, 579–585 & 2008 Nature Publishing Group All rights reserved 0307-0565/08 $30.00 www.nature.com/ijo