In summary, this study identified genes where rare coding alleles are associated with large differences in body fat distribution in humans, including an association with protection against metabolic disease for rare loss-of-function variants in the liver-expressed INHBE. Our results suggest that blocking inhibin βE may be a therapeutic approach for promoting metabolic health and uncover biological interplays between liver and adipose tissue in energy storage. This evidence concerns the gene INHBE and metabolic disease.