From modeling to measurement: Developmental trends in genetic influence on adiposity in childhood

Abstract

ObjectiveEvidence of increasing heritability of BMI over childhood can seem paradoxical given longer exposure to environmental influences. Genomic data were used to provide direct evidence of developmental increases in genetic influence.MethodsBMI standard deviation scores (BMI-SDS) at ages 4 and 10 were calculated for 2,556 twin pairs in the Twins Early Development Study. Twin analyses estimated heritability of BMI-SDS at each age and the longitudinal genetic correlation. One randomly selected twin per pair was genotyped. Genome-wide complex trait analysis (GCTA) determined DNA-based heritability at each age and the longitudinal genomic correlation. Associations with a polygenic obesity risk score (PRS) using 28 obesity-related single nucleotide polymorphisms (SNPs) were assessed at each age, with bootstrapping to test the significance of the increase in variance explained.ResultsTwin-estimated heritability increased from age 4 (0.43; 95% CI: 0.35-0.53) to 10 (0.82; 0.74-0.88). GCTA-estimated heritability went from non-significant at 4 (0.20; −0.21 to 0.61) to significant at 10 (0.29; 0.01-0.57). Longitudinal genetic correlations derived from twins (0.58) and GCTA (0.66) were similar. The same PRS explained more variance at 10 than 4 years (R2 Δ:0.024; 0.002-0.078).ConclusionsGCTA and PRS findings confirm twin-based results suggesting increasing genetic influence on adiposity during childhood despite substantial genetic stability.

Parental and child genetic contributions to obesity traits in early life based on 83 loci validated in adults: the FAMILY study

“…The increasing association between the GRS and BMI from birth to 5 years (Fig. S2) is consistent with the observation that the genetic influence on BMI becomes stronger with age over childhood . Epidemiologic studies have shown that rapid early weight gain predicts later obesity and metabolic diseases .…”

Twin studies advance the understanding of gene–environment interplay in human nutrigenomics

“…As children age and they become less dependent on their parents, the genetic effect on energy and macronutrient intakes appears to intensify, as suggested by findings in 11-to 13-year-old US twins (31 to 48 %) (8) . This pattern is similar to other health-related phenotypes, including BMI (15) , which has been recently confirmed through a more complex longitudinal genome-wide complex trait analysis for determining DNA-based heritability (16) . Heritability of dietary energy and macronutrients in adults has been found to vary widely: for energy (32 to 65 %); for fats (35 to 53 %); carbohydrates (25 to 67 %); and proteins (28 to 70 %) (6,11,12,14) .…”

Behavioral susceptibility to obesity: Gene–environment interplay in the development of weight

“…A recent meta-analysis of the heritability of BMI derived from twin studies concluded that estimates are higher in countries with higher gross domestic product (again, by inference have a more 'obesogenic' environment), and in samples with a higher average BMI [29]. We, along with others have shown that the heritability of BMI increases steadily from early childhood to late adolescence, which could reflect increasing exposure to the 'obesogenic' environment [29,30]. The findings from twin studies have been supported by molecular genetic studies, with evidence that the effects of FTO [31] and a polygenic obesity risk score [32] on BMI are significantly stronger for those born later, suggesting that genetic effects are moderated by environmental exposure.…”