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.