Abstract
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.
Design:
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 ∼1.04 kg/m2 (∼3.71 kg). Using variance components decomposition, we estimate that this single-nucleotide polymorphism accounts for ∼3% of the genetic variance in BMI in our sample (∼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 × E) interaction in both sexes and gene by parity (G × 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.
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Acknowledgements
We thank the help and support provided by many individuals at the Queensland Institute of Medical Research including the interviewers and clerical and administrative support staff supervised by Dixie Statham; Scott Gordon, Harry Beeby and David Smyth for computer support and phenotype data management; the laboratory staff for genotype sample management and genotyping, Sri Shekar for a superb introduction to QTDT; and, most of all, the twins and their relatives for their willing participation in the study. This study was supported in part by grants from NIH grants AA07535, AA07728, AA10249 and DA00272, postdoctoral training grants DA07261, MH17104 and MH14677, as well as grants from the Australian National Health and Medical Council, the Australian Associated Brewers and US Alcohol Beverage Medical Research Foundation. BKC is supported by an NHMRC Public Health Scholarship (361302). SEM is supported by an NHMRC Sidney Sax Fellowship (443036).
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Cornes, B., Lind, P., Medland, S. et al. 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 × E) interaction. Int J Obes 33, 75–79 (2009). https://doi.org/10.1038/ijo.2008.223
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DOI: https://doi.org/10.1038/ijo.2008.223
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