The association of NAFLD with sE‐selectin, independent of factors that are associated with systemic endothelial activation, was also demonstrated by the use of common NAFLD susceptibility genes, that is, PNPLA3 and GCKR. 27 Since individuals are ‘randomized’ at conception to receive an allele that either predisposes to or protects from NAFLD, these gene variants can serve as instruments to make causal inferences about the relationship between NAFLD and sE‐selectin levels. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.