Imperial College London
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ProfessorGrahamWilliams

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Professor of Endocrinology
 
 
 
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Contact

 

+44 (0)20 3313 1383graham.williams

 
 
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Location

 

10N5Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kemp:2017:10.1038/ng.3949,
author = {Kemp, JP and Morris, JA and Medina-Gomez, C and Forgetta, V and Warrington, NM and Youlten, SE and Zheng, J and Gregson, CL and Grundberg, E and Trajanoska, K and Logan, JG and Pollard, AS and Sparkes, PC and Ghirardello, EJ and Allen, R and Leitch, VD and Butterfield, NC and Komla-Ebri, D and Adoum, A-T and Curry, KF and White, JK and Kussy, F and Greenlaw, KM and Xu, C and Harvey, NC and Cooper, C and Adams, DJ and Greenwood, CMT and Maurano, MT and Kaptoge, S and Rivadeneira, F and Tobias, JH and Croucher, PI and Ackert-Bicknell, CL and Bassett, JHD and Williams, GR and Richards, JB and Evans, DM},
doi = {10.1038/ng.3949},
journal = {Nat Genet},
pages = {1468--1475},
title = {Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis.},
url = {http://dx.doi.org/10.1038/ng.3949},
volume = {49},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Osteoporosis is a common disease diagnosed primarily by measurement of bone mineral density (BMD). We undertook a genome-wide association study (GWAS) in 142,487 individuals from the UK Biobank to identify loci associated with BMD as estimated by quantitative ultrasound of the heel. We identified 307 conditionally independent single-nucleotide polymorphisms (SNPs) that attained genome-wide significance at 203 loci, explaining approximately 12% of the phenotypic variance. These included 153 previously unreported loci, and several rare variants with large effect sizes. To investigate the underlying mechanisms, we undertook (1) bioinformatic, functional genomic annotation and human osteoblast expression studies; (2) gene-function prediction; (3) skeletal phenotyping of 120 knockout mice with deletions of genes adjacent to lead independent SNPs; and (4) analysis of gene expression in mouse osteoblasts, osteocytes and osteoclasts. The results implicate GPC6 as a novel determinant of BMD, and also identify abnormal skeletal phenotypes in knockout mice associated with a further 100 prioritized genes.
AU  - Kemp,JP
AU  - Morris,JA
AU  - Medina-Gomez,C
AU  - Forgetta,V
AU  - Warrington,NM
AU  - Youlten,SE
AU  - Zheng,J
AU  - Gregson,CL
AU  - Grundberg,E
AU  - Trajanoska,K
AU  - Logan,JG
AU  - Pollard,AS
AU  - Sparkes,PC
AU  - Ghirardello,EJ
AU  - Allen,R
AU  - Leitch,VD
AU  - Butterfield,NC
AU  - Komla-Ebri,D
AU  - Adoum,A-T
AU  - Curry,KF
AU  - White,JK
AU  - Kussy,F
AU  - Greenlaw,KM
AU  - Xu,C
AU  - Harvey,NC
AU  - Cooper,C
AU  - Adams,DJ
AU  - Greenwood,CMT
AU  - Maurano,MT
AU  - Kaptoge,S
AU  - Rivadeneira,F
AU  - Tobias,JH
AU  - Croucher,PI
AU  - Ackert-Bicknell,CL
AU  - Bassett,JHD
AU  - Williams,GR
AU  - Richards,JB
AU  - Evans,DM
DO  - 10.1038/ng.3949
EP  - 1475
PY  - 2017///
SP  - 1468
TI  - Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis.
T2  - Nat Genet
UR  - http://dx.doi.org/10.1038/ng.3949
UR  - https://www.ncbi.nlm.nih.gov/pubmed/28869591
UR  - http://hdl.handle.net/10044/1/51472
VL  - 49
ER  -
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