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Life-Course Genome-...
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Medina-Gomez, C.Erasmus University Medical Center
(author)
Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
- Article/chapterEnglish2018
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LIBRIS-ID:oai:gup.ub.gu.se/264600
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https://gup.ub.gu.se/publication/264600URI
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https://doi.org/10.1016/j.ajhg.2017.12.005DOI
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https://lup.lub.lu.se/record/11dd8a80-2867-4fca-9f19-2348b1a5585cURI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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. © 2017 American Society of Human Genetics
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Added entries (persons, corporate bodies, meetings, titles ...)
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Kemp, J. P.University of Queensland,University of Bristol
(author)
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Trajanoska, K.Erasmus University Medical Center
(author)
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Luan, J.University of Cambridge
(author)
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Chesi, A.The Children's Hospital of Philadelphia
(author)
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Ahluwalia, T. S.Steno Diabetes Center Copenhagen,University of Copenhagen
(author)
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Mook-Kanamori, D. O.Leiden University Medical Centre
(author)
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Ham, A.Erasmus University Medical Center
(author)
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Hartwig, F. P.Federal University of Pelotas
(author)
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Evans, D. S.California Pacific Medical Center
(author)
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Joro, R.University of Eastern Finland,McGill University
(author)
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Nedeljkovic, I.Erasmus University Medical Center
(author)
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Zheng, H. F.McGill University
(author)
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Zhu, K.Sir Charles Gairdner Hospital,University of Western Australia, Crawley
(author)
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Atalay, M.University of Eastern Finland,National Institute on Aging, United States
(author)
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Liu, C. T.Boston University
(author)
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Nethander, Maria,1980Gothenburg University,Göteborgs universitet,Core Facilities, Bioinformatics,Core Facilities, Bioinformatics,Sahlgrenska Academy(Swepub:gu)xnetma
(author)
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Broer, L.Erasmus University Medical Center
(author)
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Porleifsson, G.deCODE Genetics
(author)
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Mullin, B. H.University of Western Australia, Crawley,Sir Charles Gairdner Hospital,University of Copenhagen
(author)
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Handelman, S. K.Wayne State University,National University Hospital of Iceland,deCODE Genetics
(author)
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Nalls, M. A.
(author)
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Jessen, L. E.University of Copenhagen,University of Ioannina,Imperial College London
(author)
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Heppe, D. H. M.Erasmus University Medical Center,Amsterdam UMC - Vrije Universiteit Amsterdam,Leiden University Medical Centre
(author)
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Richards, J. B.
(author)
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Wang, C.University of Western Australia, Crawley
(author)
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Chawes, B.University of Copenhagen,Erasmus University Medical Center
(author)
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Schraut, K. E.University of Edinburgh
(author)
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Amin, N.Erasmus University Medical Center
(author)
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Wareham, N.University of Cambridge
(author)
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Karasik, D.Bar-Ilan University
(author)
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Van der Velde, N.Erasmus University Medical Center,Academic Medical Center of University of Amsterdam (AMC)
(author)
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Ikram, M. A.Erasmus University Medical Center
(author)
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Zemel, B. S.The Children's Hospital of Philadelphia
(author)
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Zhou, Y.Boston University
(author)
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Carlsson, C. J.University of Copenhagen
(author)
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Liu, Y.Wake Forest University
(author)
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McGuigan, Fiona E.Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups(Swepub:lu)med-fam
(author)
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Boer, C. G.Erasmus University Medical Center
(author)
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Bønnelykke, K.University of Copenhagen
(author)
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Ralston, S. H.University of Edinburgh
(author)
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Robbins, J. A.University of California, San Diego
(author)
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Walsh, J. P.Sir Charles Gairdner Hospital,University of Western Australia, Crawley
(author)
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Zillikens, M. C.Erasmus University Medical Center
(author)
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Langenberg, C.University of Cambridge,University of Rochester
(author)
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Li-Gao, R.Leiden University Medical Centre
(author)
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Williams, F. M. K.King's College London
(author)
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Harris, T. B.National Institute on Aging, United States
(author)
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Akesson, KristinaLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups(Swepub:lu)orto-kak
(author)
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Jackson, R. D.Ohio State University
(author)
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Sigurdsson, G.National University Hospital of Iceland,University of Iceland
(author)
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den Heijer, M.
(author)
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van der Eerden, B. C. J.
(author)
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van de Peppel, J.Erasmus University Medical Center
(author)
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Spector, T. D.King's College London
(author)
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Pennell, C.University of Western Australia, Crawley
(author)
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Horta, B. L.Federal University of Pelotas
(author)
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Felix, J. F.Erasmus University Medical Center
(author)
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Zhao, J. H.University of Cambridge
(author)
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Wilson, S. G.Sir Charles Gairdner Hospital,University of Western Australia, Crawley,King's College London
(author)
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de Mutsert, R.Leiden University Medical Centre
(author)
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Bisgaard, H.
(author)
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Styrkársdóttir, U.deCODE Genetics
(author)
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Jaddoe, V. W.Erasmus University Medical Center,Mayo Clinic Minnesota
(author)
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Orwoll, E.Oregon Health & Science University
(author)
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Lakka, T. A.Kuopio University Hospital,University of Eastern Finland
(author)
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Scott, R.University of Cambridge
(author)
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Grant, S. F. A.The Children's Hospital of Philadelphia,University of Pennsylvania
(author)
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Lorentzon, Mattias,1970University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlomat
(author)
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van Duijn, C. M.Erasmus University Medical Center
(author)
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Wilson, J. F.
(author)
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Stefansson, K.
(author)
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Psaty, B. M.University of Washington,Kaiser Permanente Research Institute
(author)
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Kiel, D. P.Broad Institute,Beth Israel Deaconess Medical Center
(author)
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Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Sahlgrenska Academy(Swepub:gu)xohlcl
(author)
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Ntzani, E.University of Ioannina
(author)
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van Wijnen, A. J.
(author)
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Forgetta, V.McGill University
(author)
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Ghanbari, M.Erasmus University Medical Center,Mashhad University of Medical Sciences
(author)
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Logan, J. G.Imperial College London
(author)
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Williams, G. R.Imperial College London
(author)
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Bassett, J. H. D.Imperial College London
(author)
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Croucher, P. I.Garvan Institute of Medical Research
(author)
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Evangelou, E.
(author)
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Uitterlinden, A. G.Erasmus University Medical Center
(author)
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Ackert-Bicknell, C. L.
(author)
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Tobias, J. H.University of Bristol
(author)
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Evans, D. M.University of Bristol,University of Queensland
(author)
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Rivadeneira, F.Erasmus University Medical Center
(author)
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Erasmus University Medical CenterUniversity of Queensland
(creator_code:org_t)
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In:American Journal of Human Genetics: Elsevier BV102:1, s. 88-1020002-9297
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Medina-Gomez, C.
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Kemp, J. P.
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Trajanoska, K.
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Luan, J.
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Chesi, A.
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Ahluwalia, T. S.
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Mook-Kanamori, D ...
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Ham, A.
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Hartwig, F. P.
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Evans, D. S.
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Joro, R.
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Nedeljkovic, I.
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Zheng, H. F.
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Zhu, K.
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Atalay, M.
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Liu, C. T.
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Nethander, Maria ...
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Broer, L.
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Porleifsson, G.
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Mullin, B. H.
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Handelman, S. K.
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Nalls, M. A.
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Jessen, L. E.
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Heppe, D. H. M.
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Richards, J. B.
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Wang, C.
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Chawes, B.
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Schraut, K. E.
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Amin, N.
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Wareham, N.
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Boer, C. G.
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Bønnelykke, K.
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Zillikens, M. C.
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Langenberg, C.
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Li-Gao, R.
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Williams, F. M. ...
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Harris, T. B.
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Jackson, R. D.
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Sigurdsson, G.
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den Heijer, M.
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van de Peppel, J ...
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Spector, T. D.
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Pennell, C.
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Horta, B. L.
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Felix, J. F.
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Zhao, J. H.
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Wilson, S. G.
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de Mutsert, R.
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Bisgaard, H.
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Styrkársdóttir, ...
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Jaddoe, V. W.
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Orwoll, E.
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Lakka, T. A.
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Scott, R.
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Grant, S. F. A.
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Lorentzon, Matti ...
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van Duijn, C. M.
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Wilson, J. F.
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Stefansson, K.
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Psaty, B. M.
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Kiel, D. P.
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Ohlsson, Claes, ...
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Ntzani, E.
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van Wijnen, A. J ...
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Forgetta, V.
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Ghanbari, M.
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Logan, J. G.
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Williams, G. R.
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Bassett, J. H. D ...
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Croucher, P. I.
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Evangelou, E.
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Uitterlinden, A. ...
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Evans, D. M.
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