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

Abstract

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. Two-sample 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.

Keywords: Body mass index; Cirrhosis; Hepatocellular carcinoma; Mendelian randomization; Non-alcoholic fatty liver disease.