| 1. |
- Estrada, Karol, et al.
(author)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Journal article (peer-reviewed)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 2. |
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| 3. |
- Liu, Ching-Ti, et al.
(author)
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Assessment of gene-by-sex interaction effect on bone mineral density
- 2012
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In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:10, s. 2051-2064
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Journal article (peer-reviewed)abstract
- Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p?
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| 4. |
- Millán, L., et al.
(author)
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SMILES ice cloud products
- 2013
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In: Journal of Geophysical Research: Atmospheres. - : American Geophysical Union (AGU). - 2169-8996 .- 2169-897X. ; 118:12, s. 6468-6477
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Journal article (peer-reviewed)abstract
- Upper tropospheric water vapor and clouds play an important role in Earth's climate, but knowledge of them, in particular diurnal variation in deep convective clouds, is limited. An essential variable to understand them is cloud ice water content. The Japanese Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) on board the International Space Station (ISS) samples the atmosphere at different local times allowing the study of diurnal variability of atmospheric parameters. We describe a new ice cloud data set consisting of partial Ice Water Path and Ice Water Content. Preliminary comparisons with EOS-MLS, CloudSat-CPR and CALIOP-CALIPSO are presented. Then, the diurnal variation over land and over open ocean for partial ice water path is reported. Over land, a pronounced diurnal variation peaking strongly in the afternoon/early evening was found. Over the open ocean, little temporal dependence was encountered. This data set is publicly available for download in HDF5 format.
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| 5. |
- Oei, Ling, et al.
(author)
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A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
- 2014
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In: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
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Journal article (peer-reviewed)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.
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| 6. |
- Millán, P., et al.
(author)
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Sensor-network-based robust distributed control and estimation
- 2013
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In: Control Engineering Practice. - : Elsevier BV. - 0967-0661 .- 1873-6939. ; 21:9, s. 1238-1249
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Journal article (peer-reviewed)abstract
- This paper proposes a novel distributed estimation and control method for uncertain plants. It is of application in the case of large-scale systems, where each control unit is assumed to have access only to a subset of the plant outputs, and possibly controls a restricted subset of input channels. A constrained communication topology between nodes is considered so the units can benefit from estimates of neighboring nodes to build their own estimates. The paper proposes a methodology to design a distributed control structure so that the system is asymptotically driven to equilibrium with L2-gain disturbance rejection capabilities. A difficulty that arises is that the separation principle does not hold, as every single unit ignores the control action that other units might be applying. To overcome this, a two-stage design is proposed: firstly, the distributed controllers are obtained to robustly stabilize the plant despite the observation errors in the controlled output. At the second stage, the distributed observers are designed aiming to minimize the effects of the communication noise in the observation error. Both stages are formulated in terms of linear matrix inequalities. The performance is shown on a level-control real plant.
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