Separating the effects of early and later life body mass index on liver diseases: A Mendelian randomization study

Background and aim: The independent effects of childhood and adult body mass index (BMI) on non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC) are lacking assessment. We aimed to separate the effects of childhood and adult BMI on NAFLD, cirrhosis, and HCC. Methods: Genetic variants associated with childhood and adult BMI were selected as instrumental variables. Twosample univariable and multivariable MR estimated the total and direct effect of childhood and adult BMI on NAFLD, cirrhosis, and HCC. Results: Genetically predicted each 1-SD increased childhood BMI (OR = 1.30, 95 % CI = 1.12 to 1.51, P = 0.001) and adult BMI (OR = 1.57 95 % CI = 1.33 to 1.84, P = 5.49E-08) was associated with an increased risk of NAFLD. The association between childhood BMI (OR = 0.97, 95 % CI = 0.77 to 1.24, P = 0.825) and NAFLD did not remain significant after adjusting for adult BMI (OR =1.64, 95 % CI =1.23 to 2.20, P = 0.001). The direct effects of childhood and adult BMI on cirrhosis and HCC were insignificant after considering their relationship. Conclusion: Maintaining a normal BMI in adulthood significantly reduces the adverse effect of a higher childhood BMI on NAFLD. Further investigation is required to clarify the presence of this effect in cirrhosis and HCC.