After the discovery of FTO, several studies reported that its obesity-increasing effect may be attenuated in individuals who are physically active [9]–[20]. Other studies, however, were unable to replicate this interaction [21]–[26], leaving it unresolved whether physical activity (PA) can reduce FTO’s effect on obesity risk, and if so, to what extent. Identifying interactions between genetic variants and lifestyle is challenging as it requires much larger sample sizes than those needed for the detection of main effects of genes or environment [27]. Interaction studies are further hampered by the difficulty of measuring lifestyle exposures accurately, which reduces statistical power and necessitates large study sample sizes to offset this effect [28].
