Do Gene Variants Influencing Adult Adiposity Affect Birth Weight? A Population-Based Study of 24 Loci in 4,744 Danish Individuals

Abstract

BackgroundSeveral obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.Methodology/Principal FindingsMidwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10th percentile), normal (10th–90th percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.Conclusion24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life.

Characterization of the infant BMI peak: Sex differences, birth year cohort effects, association with concurrent adiposity, and heritability

“…Sovio et al (2011), for example, found that genetic variants associated with increasing obesity risk at the FTO locus were associated with earlier adiposity rebound (but not with earlier Age Peak ). Andersson et al (2010) found lower BMI Peak in individuals carrying the FTO risk genotype at rs9939609 (AA), but higher BMI later in childhood, again showing that there are complex age-dependent variations in genetic control of BMI, with lower infant BMI being characteristic of individuals at ultimately higher risk of obesity. Our results emphasize the point that while environmental factors are very important in shaping the infant BMI-for-age curve (as shown by the secular trends analysis), the majority of inter-individual variation is nonetheless attributable to genetic factors.…”

“…Given this, the infant BMI peak may be a useful trait for genetic analysis; known genetic variants associated with BMI and obesity in adults tend to associate fairly weakly with birth weight and ponderal index (Andersson et al, 2010) and with later infancy BMI (Choh et al, 2011). In contrast, a recent study using curve fitting to derive Age Peak and BMI Peak found significantly lower BMI Peak in carriers of a high risk genotype for the obesity gene FTO (Sovio et al, 2011).…”

The combined effect of MC4R and FTO risk alleles on childhood obesity in Greece

“…This finding is in accordance with other studies. 17,30,32,35,36 Elks et al report a marginal positive correlation of birth weight to the obesity-risk-allele-score, but the correlation was significantly more robust after the first 6 weeks of life. 37 The FTO and MC4R risk alleles are thought to contribute to BMI increase through regulation of central nervous system messages to the hypothalamus, regulating appetite, satiety and calorie-dense preferences.…”

Developments in Obesity Genetics in the Era of Genome-Wide Association Studies

“…While there was no significant difference in the effect sizes observed in adults and children, the effects observed for the loci in or near SEC16B , TMEM18 and KCTD15 tended to be larger in children than in adults, whereas the opposite was observed for the BDNF locus. Of interest is that there is currently no evidence that any of the established BMI loci are associated with birth weight [85,86]. …”