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APOE plays a well established role in lipid metabolism. Animal model evidence suggests  APOE  may also be associated with adiposity, but this has not been thoroughly investigated in humans. We measured adiposity (BMI, truncal fat mass, waist circumference), physical activity (PA), cardiorespiratory fitness and  APOE  genotype (E2, E3, E4) in 292 8-year-old children from the Tasmanian Infant Health Survey (TIHS), an Australian population-based prospective birth cohort. Our aims were to examine the association of  APOE  with child adiposity, and to examine the interplay between this association and other measured factors. We found that  APOE  was associated with child lipid profiles.  APOE  was also associated with child adiposity measures. The association was E4 allele-specific, with adiposity lower in the E4-containing group (BMI: Mean difference -0.90 kg/m 2 ; 95% confidence intervals (CI) -1.51, -0.28; p = 0.004). The association of  APOE4  with lower BMI differed by fitness status (difference in effect p = 0.002), and was more evident among the less fit (mean difference -1.78 kg/m 2 ; 95% CI -2.74, -0.83; p<0.001). Additionally, associations between BMI and lipids were only apparent in those of lower fitness who did not carry  APOE4 . Similar overall findings were observed when truncal fat mass and waist circumference were used as alternative adiposity measures.  APOE4  and cardiorespitatory fitness could interact to influence child adiposity. In studies addressing the genetic determinants of childhood obesity, the context of child fitness should also be taken into account.

APOE Genotype and Cardio-Respiratory Fitness Interact to Determine Adiposity in 8-Year-Old Children from the Tasmanian Infant Health Survey