An age-dependent association between variation at the @entity18957 locus and BMI in @entity1 has been suggested. We meta-analyzed associations between the @entity18957 locus ( @entity18956 ) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier @entity346 ( @entity346 ), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier @entity346 equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p=10(-20)) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p=10(-23)). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and @entity346 . Carriage of two minor alleles at @entity18956 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p=0.02), higher BMI at @entity346 (0.93% (95% CI: 0.22, 1.64), p=0.01), and earlier @entity346 (-4.72% (-5.81, -3.63), p=10(-17)), supporting cross-sectional results. Overall, we confirm the expected association between variation at @entity18956 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of @entity346 rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of @entity18957 in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between @entity346 and both later-life BMI and @entity209 risk.

Association between common variation at the XXXX locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development.

@entity1 :: ('9606', 'Species') :: ['children'] @entity18957 :: ('79068', 'Gene') :: ['FTO'] @entity18956 :: ('rs9939609', 'SNP') :: ['rs9939609'] @entity209 :: ('MESH:D008659', 'Disease') :: ['metabolic disease'] @entity346 :: ('MESH:D009759', 'Disease') :: ['adiposity rebound', 'AR']
@entity18957 :: (79068,Gene) :: ['FTO']
