Imperial College London
Portrait Picture

ProfessorGrahamWilliams

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Professor of Endocrinology
 
 
 
//

Contact

 

+44 (0)20 3313 1383graham.williams

 
 
//

Location

 

10N5Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Pereira:2020:10.7554/eLife.55549,
author = {Pereira, M and Ko, J-H and Logan, J and Protheroe, H and Kim, K-B and Tan, ALM and Croucher, PI and Park, K-S and Rotival, M and Petretto, E and Bassett, JD and Williams, GR and Behmoaras, J},
doi = {10.7554/eLife.55549},
journal = {eLife},
title = {A trans-eQTL network regulates osteoclast multinucleation and bone mass},
url = {http://dx.doi.org/10.7554/eLife.55549},
volume = {9},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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-/-, Appl2-/-, Deptor-/-) and myeloid-specific Slc40a1 knockout mice displayed abnormal bone phenotypes. We report opposing effects of MMnet genes on bone mass in mice and osteoclast multinucleation/resorption in humans with strong correlation between the two. These results identify MMnet as a functionally conserved network that regulates osteoclast multinucleation and bone mass.
AU  - Pereira,M
AU  - Ko,J-H
AU  - Logan,J
AU  - Protheroe,H
AU  - Kim,K-B
AU  - Tan,ALM
AU  - Croucher,PI
AU  - Park,K-S
AU  - Rotival,M
AU  - Petretto,E
AU  - Bassett,JD
AU  - Williams,GR
AU  - Behmoaras,J
DO  - 10.7554/eLife.55549
PY  - 2020///
SN  - 2050-084X
TI  - A trans-eQTL network regulates osteoclast multinucleation and bone mass
T2  - eLife
UR  - http://dx.doi.org/10.7554/eLife.55549
UR  - http://hdl.handle.net/10044/1/80983
VL  - 9
ER  -
Download