Childhood obesity: are genetic differences involved?

Abstract

This brief review focuses on the genetic contribution to childhood obesity. Evidence for a genetic component to excess body weight during growth is presented from the perspective of genetic epidemiology studies. Parental obesity is a predictor of childhood excess weight. The familial risk ratio for childhood obesity when a parent is obese reaches >2.5. Birth weight is characterized by a genetic heritability component on the order of 30%, with significant maternal and paternal effects in addition to the newborn genes. About 5% of childhood obesity cases are caused by a defect that impairs function in a gene, and >/=5 of these genes have been uncovered. However, the common forms of childhood obesity seem to result from a predisposition that primarily favors obesogenic behaviors in an obesogenic environment. Candidate gene and genomewide association studies reveal that these obesogenic genes have small effect sizes but that the risk alleles for obesity are quite common in populations. The latter may translate into a highly significant population-attributable risk of obesity. Gene-environment interaction studies suggest that the effects of predisposing genes can be enhanced or diminished by exposure to relevant behaviors. It is possible that the prevalence of childhood obesity is increasing across generations as a result of positive assortative mating with obese husbands and wives contributing more obese offspring than normal-weight parents.

FIGURE 1

The risk of adult obesity based on the obesity status in childhood and on parental obesity. This figure was constructed from data in reference .

FIGURE 2

Birth weight and age-adjusted adult BMI (in kg/m²). The figure was drawn from data in references and .

FIGURE 3

Mean offspring birth weight (g) for categories of paternal birth weight in selected strata of maternal birth weight. Families in which the parental birth weight was <2500 g are omitted from the figure. Birth weight was not adjusted for gestational age or prematurity. Reproduced with permission from reference .

FIGURE 4

Frequency and effect size of alleles at genes causing obesity or genes that are part of more complex oligogenic or polygenic genotypes associated with a predisposition to obesity.

FIGURE 5

Body-weight changes in monozygotic twins in response to overfeeding. The F ratio of the between-twins variance in weight gain to the within-pair variance is 3.4 (P < 0.02). Intraclass correlation for the changes is 0.55. Reproduced with permission from reference .