Associations between BMI and the FTO gene are age dependent: Results from the GINI and LISA birth cohort studies up to age 6 years

Institute of Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
Obesity Facts (Impact Factor: 2.25). 06/2010; 3(3):173-80. DOI: 10.1159/000314612
Source: PubMed


The association between polymorphisms in intron 1 of the fat mass and obesity associated gene (FTO) and obesity-related traits is one of the most robust associations reported for complex traits and is established both in adults and children. However, little is known about the longitudinal dynamics of these polymorphisms on body mass index (BMI), overweight, and obesity.
This study is based on the 2,732 full-term neonates of the German GINI-plus and LISA-plus birth cohorts, for whom genotyping data on the FTO variants rs1558902 (T>A) or rs9935401 (G>A) were available. Children were followed from birth up to age 6 years. Up to 9 anthropometric measurements of BMI were obtained. Fractional-Polynomial-Generalized-Estimation-Equation modeling was used to assess developmental trends and their potential dependence on genotype status.
We observed no evidence for BMI differences between genotypes of both variants for the first 3 years of life. However, from age 3 years onwards, we noted a higher BMI for the homozygous minor alleles carriers in comparison to the other two genotype groups. However, evidence for statistical significance was reached from the age of 4 years onwards.
This is one of the first studies investigating in detail the development of BMI depending on FTO genotype between birth and the age of 6 years in a birth cohort not selected for the phenotype studied. We observed that the association between BMI and FTO genotype evolves gradually and becomes descriptively detectable from the age of 3 years onwards.

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Available from: Thomas Illig, Nov 11, 2014
    • "The birth weight was not different among the genotypes in a Spanish study, but the statistical differences in weight and the change of weight were evident at the age of 2 weeks (the difference was 0.2 kg).[57] Most studies have shown that the effect of the gene variant appears between 3 and 7 years.[5859] A German birth cohort followed from birth to the age of 6 years revealed that the association between the FTO genotype and BMI evolved gradually, became descriptively detectable from the age of 3 years, and became significant from the age of 4 years after adjusting for gender and maternal smoking during pregnancy.[59] "
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    ABSTRACT: Genome-wide association analyses have revealed common gene variations related to obesity. Variants of the fat mass and obesity-associated (FTO) gene among more than 40 genes studied were most closely associated with obesity, but the association varies among ethnicities. Moreover, the effect is significant in people of European descent as well as Asians, but less significant among people of African descent. Although the variants were also associated with type 2 diabetes and glucose homeostasis, the associations were attenuated or abolished after adjusting for adiposity. The present review considers our current understanding of the effects of the FTO variants in different ethnic groups and in adults and children.
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    • "No association with birth weight has been observed for variants in or near TMEM18, ETV5 (SFRS10), BDNF and MC4R loci [7], [16], [17], [18], [19], [20]. While the majority of studies have found no association between variants in the FTO locus and birth weight [6], [18], [21], [22], [23], one study of 4,693 individuals found an FTO obesity risk allele to be associated with higher BMI and ponderal index at birth [20]. "
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    ABSTRACT: 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. 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. 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.
    Full-text · Article · Dec 2010 · PLoS ONE

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