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{Morris:2019:10.1038/s41588-018-0302-x,
author = {Morris, JA and Kemp, JP and Youlten, SE and Laurent, L and Logan, JG and Chai, RC and Vulpescu, NA and Forgetta, V and Kleinman, A and Mohanty, ST and Sergio, CM and Quinn, J and Nguyen-Yamamoto, L and Luco, A-L and Vijay, J and Simon, M-M and Pramatarova, A and Medina-Gomez, C and Trajanoska, K and Ghirardello, EJ and Butterfield, NC and Curry, KF and Leitch, VD and Sparkes, PC and Adoum, A-T and Mannan, NS and Komla-Ebri, DSK and Pollard, AS and Dewhurst, HF and Hassall, TAD and Beltejar, M-JG and Agee, M and Alipanahi, B and Auton, A and Bell, RK and Bryc, K and Elson, SL and Fontanillas, P and Furlotte, NA and McCreight, JC and Huber, KE and Litterman, NK and McIntyre, MH and Mountain, JL and Noblin, ES and Northover, CAM and Pitts, SJ and Sathirapongsasuti, JF and Sazonova, OV and Shelton, JF and Shringarpure, S and Tian, C and Tung, JY and Vacic, V and Wilson, CH and Adams, DJ and Vaillancourt, SM and Kaptoge, S and Baldock, P and Cooper, C and Reeve, J and Ntzani, EE and Evangel},
doi = {10.1038/s41588-018-0302-x},
journal = {Nature Genetics},
pages = {258--266},
title = {An atlas of genetic influences on osteoporosis in humans and mice},
url = {http://dx.doi.org/10.1038/s41588-018-0302-x},
volume = {51},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR) = 58, P = 1 × 10−75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P < 0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
AU  - Morris,JA
AU  - Kemp,JP
AU  - Youlten,SE
AU  - Laurent,L
AU  - Logan,JG
AU  - Chai,RC
AU  - Vulpescu,NA
AU  - Forgetta,V
AU  - Kleinman,A
AU  - Mohanty,ST
AU  - Sergio,CM
AU  - Quinn,J
AU  - Nguyen-Yamamoto,L
AU  - Luco,A-L
AU  - Vijay,J
AU  - Simon,M-M
AU  - Pramatarova,A
AU  - Medina-Gomez,C
AU  - Trajanoska,K
AU  - Ghirardello,EJ
AU  - Butterfield,NC
AU  - Curry,KF
AU  - Leitch,VD
AU  - Sparkes,PC
AU  - Adoum,A-T
AU  - Mannan,NS
AU  - Komla-Ebri,DSK
AU  - Pollard,AS
AU  - Dewhurst,HF
AU  - Hassall,TAD
AU  - Beltejar,M-JG
AU  - Agee,M
AU  - Alipanahi,B
AU  - Auton,A
AU  - Bell,RK
AU  - Bryc,K
AU  - Elson,SL
AU  - Fontanillas,P
AU  - Furlotte,NA
AU  - McCreight,JC
AU  - Huber,KE
AU  - Litterman,NK
AU  - McIntyre,MH
AU  - Mountain,JL
AU  - Noblin,ES
AU  - Northover,CAM
AU  - Pitts,SJ
AU  - Sathirapongsasuti,JF
AU  - Sazonova,OV
AU  - Shelton,JF
AU  - Shringarpure,S
AU  - Tian,C
AU  - Tung,JY
AU  - Vacic,V
AU  - Wilson,CH
AU  - Adams,DJ
AU  - Vaillancourt,SM
AU  - Kaptoge,S
AU  - Baldock,P
AU  - Cooper,C
AU  - Reeve,J
AU  - Ntzani,EE
AU  - Evangelou,E
AU  - Ohlsson,C
AU  - Karasik,D
AU  - Rivadeneira,F
AU  - Kiel,DP
AU  - Tobias,JH
AU  - Gregson,CL
AU  - Harvey,NC
AU  - Grundberg,E
AU  - Goltzman,D
AU  - Adams,DJ
AU  - Lelliott,CJ
AU  - Hinds,DA
AU  - Ackert-Bicknell,CL
AU  - Hsu,Y-H
AU  - Maurano,MT
AU  - Croucher,PI
AU  - Williams,GR
AU  - Bassett,JHD
AU  - Evans,DM
AU  - Richards,JB
DO  - 10.1038/s41588-018-0302-x
EP  - 266
PY  - 2019///
SN  - 1061-4036
SP  - 258
TI  - An atlas of genetic influences on osteoporosis in humans and mice
T2  - Nature Genetics
UR  - http://dx.doi.org/10.1038/s41588-018-0302-x
UR  - http://hdl.handle.net/10044/1/66283
VL  - 51
ER  -
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