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Genetic determinant...
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Moayyeri, Alireza
(author)
Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2014-01-14
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Oxford University Press (OUP),2014
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-228008
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-228008URI
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https://doi.org/10.1093/hmg/ddt675DOI
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https://lup.lub.lu.se/record/4552486URI
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https://gup.ub.gu.se/publication/199781URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Hsu, Yi-Hsiang
(author)
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Karasik, David
(author)
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Estrada, Karol
(author)
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Xiao, Su-Mei
(author)
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Nielson, Carrie
(author)
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Srikanth, Priya
(author)
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Giroux, Sylvie
(author)
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Wilson, Scott G.
(author)
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Zheng, Hou-Feng
(author)
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Smith, Albert V.
(author)
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Pye, Stephen R.
(author)
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Leo, Paul J.
(author)
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Teumer, Alexander
(author)
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Hwang, Joo-Yeon
(author)
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Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine(Swepub:gu)xohlcl
(author)
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McGuigan, FionaLund 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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Minster, Ryan L.
(author)
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Hayward, Caroline
(author)
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Olmos, Jose M.
(author)
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Lyytikaeinen, Leo-Pekka
(author)
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Lewis, Joshua R.
(author)
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Swart, Karin M. A.
(author)
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Masi, Laura
(author)
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Oldmeadow, Chris
(author)
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Holliday, Elizabeth G.
(author)
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Cheng, Sulin
(author)
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Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine(Swepub:gu)xmelda
(author)
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Harvey, Nicholas C.
(author)
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Kruk, Marcin
(author)
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Fabiola Del Greco, M.
(author)
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Igl, Wilmar
(author)
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Trummer, Olivia
(author)
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Grigoriou, Efi
(author)
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Luben, Robert
(author)
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Liu, Ching-Ti
(author)
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Zhou, Yanhua
(author)
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Oei, Ling
(author)
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Medina-Gomez, Carolina
(author)
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Zmuda, Joseph
(author)
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Tranah, Greg
(author)
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Brown, Suzanne J.
(author)
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Williams, Frances M.
(author)
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Soranzo, Nicole
(author)
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Jakobsdottir, Johanna
(author)
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Siggeirsdottir, Kristin
(author)
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Holliday, Kate L.
(author)
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Hannemann, Anke
(author)
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Go, Min Jin
(author)
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Garcia, Melissa
(author)
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Polasek, Ozren
(author)
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Laaksonen, Marika
(author)
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Zhu, Kun
(author)
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Enneman, Anke W.
(author)
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McEvoy, Mark
(author)
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Peel, Roseanne
(author)
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Sham, Pak Chung
(author)
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Jaworski, Maciej
(author)
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Johansson, Asa
(author)
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Hicks, Andrew A.
(author)
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Pludowski, Pawel
(author)
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Scott, Rodney
(author)
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Dhonukshe-Rutten, Rosalie A. M.
(author)
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van der Velde, Nathalie
(author)
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Kaehoenen, Mika
(author)
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Viikari, Jorma S.
(author)
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Sievaenen, Harri
(author)
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Raitakari, Olli T.
(author)
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Gonzalez-Macias, Jesus
(author)
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Hernandez, Jose L.
(author)
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Mellstroem, Dan
(author)
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Ljunggren, ÖstenUppsala universitet,Endokrinologi och mineralmetabolism(Swepub:uu)osteljun
(author)
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Cho, Yoon Shin
(author)
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Voelker, Uwe
(author)
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Nauck, Matthias
(author)
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Homuth, Georg
(author)
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Voelzke, Henry
(author)
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Haring, Robin
(author)
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Brown, Matthew A.
(author)
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McCloskey, Eugene
(author)
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Nicholson, Geoffrey C.
(author)
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Eastell, Richard
(author)
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Eisman, John A.
(author)
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Jones, Graeme
(author)
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Reid, Ian R.
(author)
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Dennison, Elaine M.
(author)
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Wark, John
(author)
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Boonen, Steven
(author)
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Vanderschueren, Dirk
(author)
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Wu, Frederick C. W.
(author)
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Aspelund, Thor
(author)
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Richards, J. Brent
(author)
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Bauer, Doug
(author)
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Hofman, Albert
(author)
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Khaw, Kay-Tee
(author)
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Dedoussis, George
(author)
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Obermayer-Pietsch, Barbara
(author)
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Gyllensten, Ulf
(author)
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Pramstaller, Peter P.
(author)
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Lorenc, Roman S.
(author)
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Cooper, Cyrus
(author)
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Kung, Annie Wai Chee
(author)
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Lips, Paul
(author)
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Alen, Markku
(author)
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Attia, John
(author)
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Luisa Brandi, Maria
(author)
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de Groot, Lisette C. P. G. M.
(author)
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Lehtimaeki, Terho
(author)
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Riancho, Jose A.
(author)
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Campbell, Harry
(author)
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Liu, Yongmei
(author)
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Harris, Tamara B.
(author)
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Åkesson, 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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Karlsson, MagnusLund 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-mka
(author)
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Lee, Jong-Young
(author)
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Wallaschofski, Henri
(author)
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Duncan, Emma L.
(author)
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O'Neill, Terence W.
(author)
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Gudnason, Vilmundur
(author)
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Spector, Timothy D.
(author)
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Rousseau, Francois
(author)
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Orwoll, Eric
(author)
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Cummings, Steven R.
(author)
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Wareham, Nick J.
(author)
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Rivadeneira, Fernando
(author)
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Uitterlinden, Andre G.
(author)
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Prince, Richard L.
(author)
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Kiel, Douglas P.
(author)
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Reeve, Jonathan
(author)
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Kaptoge, Stephen K.
(author)
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Göteborgs universitetCentre for Bone and Arthritis Research
(creator_code:org_t)
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In:Human Molecular Genetics: Oxford University Press (OUP)23:11, s. 3054-30680964-69061460-2083
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