A Quantitative Trait Locus on Chromosome 18q for Physical Activity and Dietary Intake in Hispanic Children

Abstract

Objective: Genetic components of energy homeostasis contributing to childhood obesity are poorly understood. Genome scans were performed to identify chromosomal regions contributing to physical activity and dietary intake traits in Hispanic children participating in the VIVA LA FAMILIA Study. Research Methods and Procedures: We report linkage findings on chromosome 18 for physical activity and dietary intake in 1030 siblings from 319 Hispanic families. Measurements entailed physical activity by accelerometry, dietary intake by two 24‐hour recalls, and genetic linkage analyses using SOLAR software. Results: Significant heritabilities were seen for physical activity and dietary intake, ranging from 0.46 to 0.69, except for vigorous activity (h2 = 0.18). Percentage time in sedentary activity mapped to markers D18S1102‐D18S64 on chromosome 18 [logarithm of the odds (LOD) score = 4.07], where melanocortin 4 receptor gene (MC4R) resides. Quantitative trait loci (QTLs) for total activity counts, percentage time in light or in moderate activity, and carbohydrate intake and percentage of energy intake from carbohydrates were detected in the same region (LOD = 2.28, 2.79, 2.2, 1.84, and 1.51, respectively). A novel loss of function mutation in MC4R (G55V) was detected in six obese relatives, but not in the rest of the cohort. Removal of these MC4R‐deficient subjects from the analysis reduced the LOD score for sedentary activity to 3.94. Discussion: Given its role in the regulation of food intake and energy expenditure, MC4R is a strong positional candidate gene for the QTL on chromosome 18 detected for physical activity and dietary intake in Hispanic children.

Heritability and genetic etiology of habitual physical activity: a twin study with objective measures

“…This is lower than the 78 % observed earlier by Joosen et al , but is congruent with the 55 % observed in a twin study with subjective (Mustelin et al 2009) measures of physical activity, but higher than the 37 % of the twin study with objective measurements (den Hoed et al 2013). In concordance with earlier studies, the present study suggests that the residual variance (43 %) is likely accounted for by unique environmental factors (AE model) (Cai et al 2006;Joosen et al 2005;Mustelin et al 2009;den Hoed et al 2013). However, a role for common environmental factors (ACE model) cannot be excluded, as approximately 262 twin pairs are required to detect such an effect with an additive genetic effect of 60 %, a confidence level of 0.05 and a power of 80 % (Visscher et al 2008).…”

“…In fact, evidence from twin studies with objective measures of physical activity suggests a minor genetic effect in children (Fisher et al 2010), a high level of heritability (h 2 = 78 %) in young adults , whereas a heritability of 35 % was estimated in a large sample of women ranging from 18 to 80 years of age (den Hoed et al 2013). Studies aiming to identify genetic variants that are associated with objective measures of HPA are scarce (Cai et al 2006).…”

Driven to Be Inactive?—The Genetics of Physical Activity

“…Furthermore, a study of Hispanic children that measured physical activity using accelerometry suggested that a mutation of MC4R , which colocalized to a QTL for chromosome 18q, was associated with activity levels. 64 However, MC4R did not colocalize to any of the QTL identified in the larger human GWAS 66 or in any of the identified animal QTL. Thus, while MC4R shows promise as a candidate gene, further evidence is needed.…”

“…In an earlier, smaller genome-wide scans in humans, Cai and coworkers 64 identified one highly significant QTL on chromosome 18q associated with sedentary activity in Hispanic American children. Colocalizing within this QTL, the authors suggested that the melanocortin-4 receptor ( MC4R ) gene was a potential gene linked with physical activity in their cohort.…”

“…85 However, Nhlh2 is known to have transcriptional control of MC4R , 80 of which polymorphisms in the MC4R gene have been associated with obesity and reduced physical activity in several studies. 64,69,86 An example of this association was shown in the Quebec Family Study where the inactive offspring in the cohort that had the MC4R-C-2745T variant had a lower body mass index (BMI); however, there was no association between inactivity and BMI in the parents. 69 While associated with MC4R , the Nhlh2 gene is also known to be associated with leptin, a key regulator of food intake and energy expenditure.…”