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{Medina-Gomez:2018:10.1016/j.ajhg.2017.12.005,
author = {Medina-Gomez, C and Kemp, JP and Trajanoska, K and Luan, J and Chesi, A and Ahluwalia, TS and Mook-Kanamori, DO and Ham, A and Hartwig, FP and Evans, DS and Joro, R and Nedeljkovic, I and Zheng, H-F and Zhu, K and Atalay, M and Liu, C-T and Nethander, M and Broer, L and Porleifsson, G and Mullin, BH and Handelman, SK and Nalls, MA and Jessen, LE and Heppe, DHM and Richards, JB and Wang, C and Chawes, B and Schraut, KE and Amin, N and Wareham, N and Karasik, D and Van, der Velde N and Ikram, MA and Zemel, BS and Zhou, Y and Carlsson, CJ and Liu, Y and McGuigan, FE and Boer, CG and Bønnelykke, K and Ralston, SH and Robbins, JA and Walsh, JP and Zillikens, MC and Langenberg, C and Li-Gao, R and Williams, FMK and Harris, TB and Akesson, K and Jackson, RD and Sigurdsson, G and den, Heijer M and van, der Eerden BCJ and van, de Peppel J and Spector, TD and Pennell, C and Horta, BL and Felix, JF and Zhao, JH and Wilson, SG and de, Mutsert R and Bisgaard, H and Styrkársdóttir, U and Jaddoe, VW },
doi = {10.1016/j.ajhg.2017.12.005},
journal = {AJHG},
pages = {88--102},
title = {Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.},
url = {http://dx.doi.org/10.1016/j.ajhg.2017.12.005},
volume = {102},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.
AU  - Medina-Gomez,C
AU  - Kemp,JP
AU  - Trajanoska,K
AU  - Luan,J
AU  - Chesi,A
AU  - Ahluwalia,TS
AU  - Mook-Kanamori,DO
AU  - Ham,A
AU  - Hartwig,FP
AU  - Evans,DS
AU  - Joro,R
AU  - Nedeljkovic,I
AU  - Zheng,H-F
AU  - Zhu,K
AU  - Atalay,M
AU  - Liu,C-T
AU  - Nethander,M
AU  - Broer,L
AU  - Porleifsson,G
AU  - Mullin,BH
AU  - Handelman,SK
AU  - Nalls,MA
AU  - Jessen,LE
AU  - Heppe,DHM
AU  - Richards,JB
AU  - Wang,C
AU  - Chawes,B
AU  - Schraut,KE
AU  - Amin,N
AU  - Wareham,N
AU  - Karasik,D
AU  - Van,der Velde N
AU  - Ikram,MA
AU  - Zemel,BS
AU  - Zhou,Y
AU  - Carlsson,CJ
AU  - Liu,Y
AU  - McGuigan,FE
AU  - Boer,CG
AU  - Bønnelykke,K
AU  - Ralston,SH
AU  - Robbins,JA
AU  - Walsh,JP
AU  - Zillikens,MC
AU  - Langenberg,C
AU  - Li-Gao,R
AU  - Williams,FMK
AU  - Harris,TB
AU  - Akesson,K
AU  - Jackson,RD
AU  - Sigurdsson,G
AU  - den,Heijer M
AU  - van,der Eerden BCJ
AU  - van,de Peppel J
AU  - Spector,TD
AU  - Pennell,C
AU  - Horta,BL
AU  - Felix,JF
AU  - Zhao,JH
AU  - Wilson,SG
AU  - de,Mutsert R
AU  - Bisgaard,H
AU  - Styrkársdóttir,U
AU  - Jaddoe,VW
AU  - Orwoll,E
AU  - Lakka,TA
AU  - Scott,R
AU  - Grant,SFA
AU  - Lorentzon,M
AU  - van,Duijn CM
AU  - Wilson,JF
AU  - Stefansson,K
AU  - Psaty,BM
AU  - Kiel,DP
AU  - Ohlsson,C
AU  - Ntzani,E
AU  - van,Wijnen AJ
AU  - Forgetta,V
AU  - Ghanbari,M
AU  - Logan,JG
AU  - Williams,GR
AU  - Bassett,JHD
AU  - Croucher,PI
AU  - Evangelou,E
AU  - Uitterlinden,AG
AU  - Ackert-Bicknell,CL
AU  - Tobias,JH
AU  - Evans,DM
AU  - Rivadeneira,F
DO  - 10.1016/j.ajhg.2017.12.005
EP  - 102
PY  - 2018///
SN  - 0002-9297
SP  - 88
TI  - Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.
T2  - AJHG
UR  - http://dx.doi.org/10.1016/j.ajhg.2017.12.005
UR  - http://hdl.handle.net/10044/1/56081
VL  - 102
ER  -
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