Aims/hypotheses We recently reported significant associations between BMI and three TUB single nucleotide polymorphisms (SNPs) in two Dutch cohorts enriched for type 2 diabetes. Here, we attempted a replication of these associations in a large population-based cohort of female twins comprehensively phenotyped for measures of general and central obesity. Methods Two TUB SNPs (rs2272382, rs2272383) and a third (rs1528133), 22 kb distal to RIC3, were genotyped in 2694 Europid women from the St Thomas' UK Adult Twin Registry (Twins UK) (mean age +/- SD: 47.6 +/- 12.7 years; 42.8% postmenopausal). We explored the hypothesis that TUB is a candidate gene for late-onset obesity in humans through testing the interaction of the SNPs by menopausal status. Results In the whole cohort, none of the three SNPs showed a significant main effect on measures of general or central obesity. However, for central obesity the rs2272382 SNP showed a significant interaction with menopausal status (p=0.036). Postmenopausal women omozygous for the minor allele of rs2272382 showed significantly more general obesity (p=0.022) and central obesity (p=0.009) than carriers of the major allele. Differences (beta [95% CI]) between the two genotype groups were 0.92 kg/m(2) (0.03-1.81) for BMI (p=0.036), 2.73 cm (0.62-4.84) for waist circumference (p=0.013) and 2.43% (0.27-4.60) for per cent central fat (p=0.027). These associations were confirmed by a sibling transmission disequilibrium test for central obesity, waist circumference and per cent central fat. Conclusions/interpretation We have replicated associations of TUB SNP rs2272382 with measures of general and central obesity in normal postmenopausal women. These findings confirm TUB as a candidate gene for late-onset obesity in humans.