Gene expression signature of obesity in monozygotic twins

Objective: Observational studies suggest that obesity might have a Mendelian origin, but it is not clear if gene expression patterns observed in obese subjects are secondary to genetic traits or not. Approach: Here we test a transcriptomic signature of obesity previously identified by our group on a large cohort of twin subjects (TwinsUK). Main results: The results show that the signature correlates strongly both with body mass index (BMI) and fat mass. Moreover, in paired transcriptomes of monozygotic twins, changes in signature correlate with changes in BMI and fat mass. We also identify a set of deregulated pathways involved in obesity, from inflammation to metabolism, and show that their pathway deregulation score is strongly correlated with BMI variations in pairs of identical twins. Significance: Taken together, our results strongly indicate that alterations in gene expression observed in obese subjects are not due to their genetic background, and should therefore primarily be associated with environment and lifestyle.