The impact of genetic variants on BMI increase during childhood versus adulthood

Genetic variants that predispose individuals to obesity may have differing influences during childhood versus adulthood, and additive effects of such variants are likely to occur. Our ongoing studies to identify genetic determinants of obesity in American Indians have identified 67 single-nucleotide polymorphisms (SNPs) that reproducibly associate with maximum lifetime non-diabetic body mass index (BMI). This study aimed to identify when, during the lifetime, these variants have their greatest impact on BMI increase.

A total of 5906 Native Americans of predominantly Pima Indian heritage with repeated measures of BMI between the ages of 5 and 45 years were included in this study. The association between each SNP with the rates of BMI increase during childhood (5-19 years) and adulthood (20-45 years) were assessed separately. The significant SNPs were used to calculate a cumulative allelic risk score (ARS) for childhood and adulthood, respectively, to assess the additive effect of these variants within each period of life.

The majority of these SNPs (36 of 67) were associated with rate of BMI increase during childhood (P-value range: 0.00004-0.05), whereas only nine SNPs were associated with rate of BMI change during adulthood (P-value range: 0.002-0.02). These 36 SNPs associated with childhood BMI gain likely had a cumulative effect as a higher childhood-ARS associated with rate of BMI change (β=0.032 kg m(-2) per year per risk allele, 95% confidence interval: 0.027-0.036, P<0.0001), such that at age 19 years, individuals with the highest number of risk alleles had a BMI of 10.2 kg m(-2) greater than subjects with the lowest number of risk alleles.

Overall, our data indicates that genetic polymorphisms associated with lifetime BMI may influence the rate of BMI increase during different periods in the life course. The majority of these polymorphisms have a larger impact on BMI during childhood, providing further evidence that prevention of obesity will need to begin early in life.