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Title: A QTL on Chromosome 18q influences energy intake and expenditure in Hispanic children: the VIVA LA FAMILIA study

Author
item CAI, GUOWEN - SWF BIOMED RES, SAN ANTON
item Butte, Nancy
item COLE, SHELLEY - SWF BIOMED RES, SAN ANTON
item FAROOQI, SADAF - UNIV OF CAMBRIDGE UK
item GORING, HAROLD - SWF BIOMED RES, SAN ANTON
item DIEGO, VINCE - SWF BIOMED RES, SAN ANTON
item O'RAHILLY, STEVEN - UNIV OF CAMBRIDGE UK
item COMUZZIE, ANTHONY - SWF BIOMED RES, SAN ANTON

Submitted to: Obesity
Publication Type: Abstract Only
Publication Acceptance Date: 3/20/2005
Publication Date: 9/4/2005
Citation: Cai, G., Butte, N., Cole, S., Farooqi, S., Goring, H., Diego, V., O'Rahilly, S., Comuzzie, A. 2005. A QTL on chromosome 18q influences energy intake and expenditure in Hispanic children: the VIVA LA FAMILIA study [abstract]. Obesity. 13:A9.

Interpretive Summary:

Technical Abstract: The genetic contribution to dysregulation of energy intake and/or energy expenditure contributing to common obesities in children is poorly understood. A genome scan was performed to identify chromosomal regions contributing to obesity-related traits in Hispanic children participating in the VIVA LA FAMILIA study. Herewithin, we report linkage findings on chromosome 18 for diet and energy expenditure in 465 overweight and non-overweight Hispanic siblings. Total energy expenditure (TEE) and its components sleeping metabolic rate (SMR) and spontaneous physical activity (SPA) were measured using 24-h room respiration calorimetry, free-living physical activity was assessed using 3-d accelerometer monitoring, and dietary intake was assessed by two 24-h dietary recalls. Genetic linkage analyses were conducted using SOLAR software. SMR, SPA, total activity counts and percent time in moderate activity were heritable, with heritabilities ranging from 0.41 to 0.70 (p<0.000001). Genome-wide scans of SPA mapped to marker D18S68 on chromosome 18 with a LOD score of 3.35, where melanocortin receptor gene (MCR4) locates. Quantitative trait loci (QTLs) for SMR, total activity counts and percent time in moderate activity also were detected at this same marker (LOD=1.25, 1.62, and 1.85, respectively), as well as for dietary intakes of total protein and carbohydrate (LOD=1.95 and 2.04, respectively). A novel mutation (G55V) in MCR4 gene was detected in three related children. Removal of these subjects from the SPA analysis reduced the LOD score to 2.59. These results suggest that a QTL on chromosome 18q contributes to the variation of energy intake and expenditure in Hispanic children. Given its role in regulation of food intake and energy expenditure, MCR4 gene is a strong positional candidate gene for the QTL detected in this cohort of Hispanic children.