The effect of liver enzymes on adiposity: a Mendelian randomization study
Poorer liver function is positively associated with diabetes in Mendelian randomization (MR) studies. Observationally, adiposity is associated with poorer liver function. To clarify the etiology, we assessed the association of liver function with adiposity observationally and using two sample MR for validation.\n\nIn the \"Children of 1997\" birth cohort, we used multivariable linear regression to assess the associations of ALT and alkaline phosphatase (ALP) (IU/L) at [~]17.5 years with body mass index (BMI) (kg/m2). Using MR, genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) (100% change in concentration), were applied to genome-wide association studies of BMI, waist circumference (WC) and waist-hip ratio (WHR) (standard deviations) to obtain unconfounded inverse-variance weighting estimates.\n\nObservationally, ALT was positively associated with BMI (0.10, 95% confidence interval (CI) 0.09 to 0.11). ALP was inversely associated with BMI (-0.018, 95% CI -0.024 to -0.012). Using MR, ALT was inversely associated with BMI (-0.14, 95% CI -0.20 to -0.07), but not WC or WHR. ALP and GGT were unrelated to adiposity.\n\nPoorer liver function might not cause adiposity; instead higher ALT might reduce BMI. Whether ALT contributes to diabetes by reducing muscle mass, given the no association of ALT with WC or WHR, requires investigation.\n\nAbbreviations