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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Rzehak
Peter
P
Institute of Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany. peter.rzehak@helmholtz-muenchen.de
Scherag
André
A
Grallert
Harald
H
Sausenthaler
Stefanie
S
Koletzko
Sibylle
S
Bauer
Carl Peter
CP
Schaaf
Beate
B
von Berg
Andrea
A
Berdel
Dietrich
D
Borte
Michael
M
Herbarth
Olf
O
Krämer
Ursula
U
Illig
Thomas
T
Wichmann
H-Erich
HE
Hebebrand
Johannes
J
Heinrich
Joachim
J
D017677:Age Distribution; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012044:Regression Analysis
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human