Associations between BMI and the FTO gene are age dependent: results from the GINI and LISA birth cohort studies up to age 6 years.
ABSTRACT 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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ABSTRACT: Numerous chronic diseases in childhood and adulthood have their origins in perinatal life and are potentially influenced by trans-generational epigenetic processes. Therefore, prospective birth cohorts can substantially contribute to our knowledge about the etiology of diseases including modifiable risk factors. The two population-based German birth cohorts GINIplus and LISAplus aim to describe the natural course of chronic diseases and intermediate phenotypes in childhood and its determinants, and to identify potential genetic effect modifications. In the mid-1990s, 5,991 (GINIplus) and 3,097 (LISAplus) healthy, term newborns were recruited for long-term follow-up in four regions of Germany. The follow-up rate for the first 10 years was about 55%. We analyzed the growth and development of overweight, infections and allergic diseases, mental and oral health, metabolic and inflammatory parameters and the role of potential risk factors including genetics. The results of these two birth cohorts substantially contribute to the current knowledge about the natural course of these health parameters. These data were included in many international projects and consortia for purposes of international comparisons of prevalence and consistency of findings, and to increase the power of the analyses.Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 06/2012; 55(6-7):864-74. · 0.72 Impact Factor
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ABSTRACT: We investigated cross-sectionally and longitudinally the relationship between FTO rs9939609 and obesity-related characteristics in the European children of the IDEFICS project and the interaction of this variant with a lifestyle intervention. A cohort of 16224 children (2-9 years) was recruited into a population-based survey (T0) from eight European countries. A second survey (T1) reassessed the children two years later. A random sample of 4405 children was extracted for genetic studies. 3168 children were re-examined two years later. Half of them underwent a lifestyle intervention program. The FTO rs9939609 was genotyped. Weight, height, waist circumference, triceps and subscapular skinfolds were measured at T0 and T1. At T0, the risk A allele of rs9939609 was significantly associated with higher values of body mass index (BMI), waist circumference and skinfolds (age, sex, and country-adjusted p-values: all p<0.001) and with a statistically significant increased risk of overweight/obesity. Over the two year follow-up, no interaction between genotype and intervention was observed. The A allele was associated to a significantly higher increase in all the anthropometric variables examined at T0 independently from the study group (intervention versus control) (p-values: all p<0.002, adjusted for age, sex, country, intervention/control study group, T0 values, and individual time interval between T0 and T1). Over the two-year follow-up, 210 new cases of overweight/obesity occurred. A statistically significant higher incidence of overweight/obesity was associated to the A allele [OR(A) = 1.95, 95% CI = (1.29; 2.97)]. We confirmed the association between the FTO rs9939609 and body mass and overweight/obesity risk in European children. The main finding of the study is that the A allele carriers present higher increase of body mass and central adiposity over time and higher risk of developing overweight/obesity during growth, independently from intervention measures.PLoS ONE 01/2012; 7(11):e48876. · 3.73 Impact Factor
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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.Indian journal of endocrinology and metabolism. 12/2012; 16(Suppl 3):S588-95.