33 research outputs found

    Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies

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    OBJECTIVE: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. METHODS: A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10(-5) were considered significant. RESULTS: SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(-5) , odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10(-5) , OR 0.82, 95% CI 0.74-0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10(-5) , OR 0.87, 95% CI 0.82-0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10(-5) , OR 0.85, 95% CI 0.79-0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. CONCLUSION: Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated

    Solar Spectroscopy and (Pseudo-)Diagnostics of the Solar Chromosphere

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    I first review trends in current solar spectrometry and then concentrate on comparing various spectroscopic diagnostics of the solar chromosphere. Some are actually not at all chromospheric but just photospheric or clapotispheric and do not convey information on chromospheric heating, even though this is often assumed. Balmer Halpha is the principal displayer of the closed-field chromosphere, but it is unclear how chromospheric fibrils gain their large Halpha opacity. The open-field chromosphere seems to harbor most if not all coronal heating and solar wind driving, but is hardly seen in optical diagnostics.Comment: To appear in "Recent Advances in Spectroscopy: Astrophysical, Theoretical and Experimental Perspectives", eds. R.K. Chaudhuri, M.V. Mekkaden, A.V. Raveendran and A. Satya Narayanan, Astrophysics and Space Science Proceedings, Springer, Heidelberg, 2009. Revision: references corrected, new references added, minor text correction

    The genetic epidemiology of joint shape and the development of osteoarthritis

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    Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

    The Rotterdam Study: 2016 objectives and design update

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