A trans-eQTL network regulates osteoclast multinucleation and bone mass.

ABSTRACT: Functional characterisation of cell-type-specific regulatory networks is key to establish a causal link between genetic variation and phenotype. The osteoclast offers a unique model for interrogating the contribution of co-regulated genes to in vivo phenotype as its multinucleation and resorption activities determine quantifiable skeletal traits. Here we took advantage of a trans-regulated gene network (MMnet, macrophage multinucleation network) which we found to be significantly enriched for GWAS variants associated with bone-related phenotypes. We found that the network hub gene Bcat1 and seven other co-regulated MMnet genes out of 13, regulate bone function. Specifically, global (Pik3cb^-/-, Atp8b2^+/-, Igsf8^-/-, Eml1<

SUBMITTER: Pereira M 

PROVIDER: S-EPMC7351491 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature