Replication of the association of common rs9939609 variant of FTO with increased BMI in an Australian adult twin population but no evidence for gene by environment (G x E) interaction.
OBJECTIVE
To further investigate a common variant (rs9939609) in the fat mass- and obesity-associated gene (FTO), which recent genome-wide association studies have shown to be associated with body mass index (BMI) and obesity.


METHODS
We examined the effect of this FTO variant on BMI in 3353 Australian adult male and female twins.


RESULTS
The minor A allele of rs9939609 was associated with an increased BMI (P=0.0007). Each additional copy of the A allele was associated with a mean BMI increase of approximately 1.04 kg/m(2) (approximately 3.71 kg). Using variance components decomposition, we estimate that this single-nucleotide polymorphism accounts for approximately 3% of the genetic variance in BMI in our sample (approximately 2% of the total variance). By comparing intrapair variances of monozygotic twins of different genotypes we were able to perform a direct test of gene by environment (G x E) interaction in both sexes and gene by parity (G x P) interaction in women, but no evidence was found for either.


CONCLUSIONS
In addition to supporting earlier findings that the rs9939609 variant in the FTO gene is associated with an increased BMI, our results indicate that the associated genetic effect does not interact with environment or parity.
Cornes
B K
BK
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. belinda.cornes@gmail.com
Lind
P A
PA
Medland
S E
SE
Montgomery
G W
GW
Nyholt
D R
DR
Martin
N G
NG
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001315:Australia; D015992:Body Mass Index; D016009:Chi-Square Distribution; D005060:Europe / Q000208:ethnology; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008019:Life Style; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010298:Parity; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D012737:Sex Factors; D014427:Twins / Q000235:genetics*
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human