Do gene variants influencing adult adiposity affect birth weight? A population-based study of 24 loci in 4,744 Danish individuals

Abstract

Background: Several 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 findings: Midwife 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 (≤10(th) percentile), normal (10(th)-90(th) 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.

Conclusion: 24 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.

Figure 1. Individual associations between obesity risk variants and BMI, birth weight and ponderal index in the subsample of Inter99 with birth weight data available (n = 4,213).

Effect sizes and 95%CI are giving as z-scores. The variants are ordered according to their effect on adult BMI and their effects are given for the allele previously reported to increase adult adiposity. Black dots and lines indicate statistically significant associations (p<0.05), whereas grey indicate non-significant. General linear models assuming additive genetic models are applied for all variants. Analyses of BMI are adjusted for age and sex. Analyses of birth weight and ponderal index are adjusted for sex, maternal diabetes status and parity. CI; confidence interval.

Figure 2. Boxplot showing the number of obesity risk alleles in individuals with low, normal and high birth weight, respectively (n = 2,926).

The black line is the median number of risk alleles, the grey boxes represent the interquartile range and the whiskers denote the range of risk alleles within each group. Individuals with low birth weight (n = 338) were born at or below the sex-specific 10^th percentile of birth weight in the Inter99 population, while individuals with high birth weight (n = 325) were born at or above the sex-specific 90^th percentile of birth weight.