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dc.contributor.authorMoayyeri, Aes_ES
dc.contributor.authorHsu, YUes_ES
dc.contributor.authorKarasik, Des_ES
dc.contributor.authorEstrada, Kes_ES
dc.contributor.authorXiao, SMes_ES
dc.contributor.authorNielson, Ces_ES
dc.contributor.authorSrikanth, Pes_ES
dc.contributor.authorGiroux, Ses_ES
dc.contributor.authorWilson, SGes_ES
dc.contributor.authorZheng, HFes_ES
dc.contributor.authorSmith, AVes_ES
dc.contributor.authorPye, SRes_ES
dc.contributor.authorLeo, Paul J.es_ES
dc.contributor.authorTeumer, Aes_ES
dc.contributor.authorHwang, JYes_ES
dc.contributor.authorOhlsson, Ces_ES
dc.contributor.authorMcGuigan, Fes_ES
dc.contributor.authorMinster, Rles_ES
dc.contributor.authorHayward, Ces_ES
dc.contributor.authorOlmos Martínez, José Manuel es_ES
dc.contributor.authorGonzález Macías, Jesús es_ES
dc.contributor.authorHernández Hernández, José Luis es_ES
dc.contributor.authorRiancho Moral, José Antonio es_ES
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractQuantitative 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 × 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 × 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 × 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.es_ES
dc.format.extent15 p.es_ES
dc.publisherOxford University Presses_ES
dc.rightsAtribución-NoComercial 3.0 España*
dc.sourceHum Mol Genet. 2014 Jun 1;23(11):3054-68es_ES
dc.titleGenetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortiumes_ES

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Atribución-NoComercial 3.0 EspañaExcept where otherwise noted, this item's license is described as Atribución-NoComercial 3.0 España