Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Oei, L; Hsu, YH; Styrkarsdottir, U; Eussen, BH; de, Klein, A; Peters, MJ; Halldorsson, B; Liu, CT; Alonso, N; Kaptoge, SK; Thorleifsson, G; Hallmans, G; Hocking, LJ; Husted, LB; Jameson, KA; Kruk, M; Lewis, JR; Patel, MS; Scollen, S; Svensson, O; Trompet, S; van, Schoor, NM; Zhu, K; Buckley, BM; Cooper, C; Ford, I; Goltzman, D; González-Macías, J; Langdahl, BL; Leslie, WD; Lips, P; Lorenc, RS; Olmos, JM; Pettersson-Kymmer, U; Reid, DM; Riancho, JA; Slagboom, PE; Garcia-Ibarbia, C; Ingvarsson, T; Johannsdottir, H; Luben, R; Medina-Gómez, C; Arp, P; Nandakumar, K; Palsson, ST; Sigurdsson, G; van, Meurs, JB; Zhou, Y; Hofman, A; Jukema, JW; Pols, HA; Prince, RL; Cupples, LA; Marshall, CR; Pinto, D; Sato, D; Scherer, SW; Reeve, J; Thorsteinsdottir, U; Karasik, D; Richards, JB; Stefansson, K; Uitterlinden, AG; Ralston, SH; Ioannidis, JP; Kiel, DP; Rivadeneira, F; Estrada, K.
A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus.
J Med Genet. 2014; 51(2): 122-31.
Doi: 10.1136/jmedgenet-2013-102064
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Alonso Lopez Nerea
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- Abstract:
- BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. AIM: To identify CNVs associated with osteoporotic bone fracture risk. METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p = 8.69 × 10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p = 0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk. CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
- Find related publications in this database (using NLM MeSH Indexing)
- Case-Control Studies - administration & dosage
- Chromosome Breakpoints - administration & dosage
- Chromosomes, Human, Pair 6 - genetics
- Cohort Studies - administration & dosage
- DNA Copy Number Variations - administration & dosage
- DNA Mutational Analysis - administration & dosage
- Gene Deletion - administration & dosage
- Gene Dosage - administration & dosage
- Genome-Wide Association Study - administration & dosage
- Humans - administration & dosage
- Markov Chains - administration & dosage
- Middle Aged - administration & dosage
- Osteoporosis - genetics
- Osteoporotic Fractures - genetics
- Find related publications in this database (Keywords)
- Osteoporosis
- Copy-Number
- Calcium and Bone
- Genetic Epidemiology
- Genome-Wide