This study shows that recently established genetic variants for adult BMI have a combined association with childhood weight gain that is apparent even within the first weeks from birth. The combined association between these variants and childhood BMI, of around 0.5 SDS between the lowest and highest allele risk score groups, was similar in size to that seen with adult BMI (1.5 kg/m2
) in terms of proportion of a standard deviation 
. Therefore, while these risk variants may well influence rate of weight gain in adults 
, we postulate that that their relative influence on the rate of weight gain may be greater during childhood.
Their association with weight gain was already apparent from birth, within the first 6 weeks of life, and these adult obesity risk alleles were, in combination, protective against poor weight gain during the first weeks of life after birth. These findings are striking considering that these variants were originally discovered by association with adult BMI or obesity in populations with mean ages ranging from 40 to 60+ years 
. Other obesity susceptibility variants in/near MAF
, and PTER 
have been identified in other GWA studies of early-onset and severe obesity, and putative associations with early life weight gain may be more expected with those variants. In addition, we observed that the adult obesity risk alleles were also associated with faster gains in length/height during infancy, but not during childhood. These findings are consistent with the Karlberg model of the endocrine regulation of childhood growth, whereby early infancy growth in length/height is largely controlled by nutritional factors, while the relatively stable trajectory of childhood growth reflects the setting of the growth hormone–insulin-like growth factor–I axis 
. This potential weight-regulated drive in length gain likely explains the concurrent gains in both length and weight during infancy. Consequently, the obesity-risk-allele score showed a weaker association with BMI than with weight until age 3.5 years.
Rapid infancy weight gain and larger infant body weight have been consistently related to increased risk of obesity in subsequent childhood or adult life 
. However, life-course disease studies in historical cohort studies have provided conflicting evidence. For example, rapid infant weight gain has been associated with increased risk of obesity and the metabolic syndrome, but with reduced risk of type 2 diabetes 
. One difficulty is that studies in historical cohorts or in societies that are undergoing nutritional transition may identify life-course associations that are specific to those particular settings 
. Even in contemporary western studies, the very long-term follow-up needed to record adult disease outcomes may mean that current findings will not be applicable to future infant settings. We propose that the application in contemporary birth cohorts of genetic markers that are robustly associated with adult disease risks may provide a novel approach to life-course epidemiology, by identifying early exposures that are directly relevant to current settings.
Infancy weight gain and growth are markedly influenced by nutritional factors, such as type of milk feeding 
. Our current findings show that genetic factors also contribute to early weight gain and growth. While the mechanisms of action for these obesity variants have yet to be established, many show high levels of expression, or have known actions, in the central nervous system and could therefore regulate feeding behaviour 
. However, there is likely to be heterogeneity in their biological actions and in their specific effects during childhood and infancy. Future identification of the biological actions related to individual variants will shed further light on the specific early life mechanisms that lead to obesity. However, in view of their modest effect sizes, much larger studies or collaborations to pool longitudinal data from multiple birth cohorts will be needed to distinguish the specific childhood manifestations of individual variants.
Failure to thrive in infancy, variably defined as underweight or poor weight gain, is a multifactorial condition 
. After exclusion of a wide range of medical conditions, nonorganic failure to thrive was traditionally considered to be a risk marker for maternal rejection and neglect 
. However, the majority of infants with failure to thrive likely represent the lower-normal distribution of infancy weight gain. Health professionals have increasingly recognised the important contribution of innate differences in infant food intake rather than simply food provision by the caregiver 
, but until now no such infant factors have been demonstrated. We postulate that genetic factors in the infant that increase appetite and predispose to later obesity are protective against infant failure to thrive.
In conclusion, greater early infancy gains in weight and length represent the start of pathway to adult obesity risk in contemporary settings. Our findings demonstrate the utility of using robust genetic markers of disease risk to identify life-course disease associations with current relevance.