Genetic markers of obesity risk: stronger associations with body composition in overweight compared to normal-weight children.

Genetic factors are important determinants of overweight. We
examined whether there are differential effect sizes depending on
children's body composition. We analysed data of n = 4,837 children
recorded in the Avon Longitudinal Study of Parents and Children
(ALSPAC), applying quantile regression with sex- and age-specific
standard deviation scores (SDS) of body mass index (BMI) or with
body fat mass index and fat-free mass index at 9 years as outcome
variables and an "obesity-risk-allele score" based on eight genetic
variants known to be associated with childhood BMI as the
explanatory variable. The quantile regression coefficients
increased with increasing child's BMI-SDS and fat mass index
percentiles, indicating larger effects of the genetic factors at
higher percentiles. While the associations with BMI-SDS were of
similar size in medium and high BMI quantiles (40th percentile and
above), effect sizes with fat mass index increased over the whole
fat mass index distribution. For example, the fat mass index of a
normal-weight (50th percentile) child was increased by 0.13 kg/m(2)
(95% confidence interval (CI): 0.09, 0.16) per additional allele,
compared to 0.24 kg/m(2) per allele (95% CI: 0.15, 0.32) in
children at the 90th percentile. The genetic associations with
fat-free mass index were weaker and the quantile regression effects
less pronounced than those on fat mass index. Genetic risk factors
for childhood overweight appear to have greater effects on fatter
children. Interaction of known genetic factors with environmental
or unknown genetic factors might provide a potential explanation of
these findings.