| 1. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 2. |
- Visscher, Corinne, et al.
(författare)
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A multicentre study to diagnostic accuracy of temporomandibular pain tests
- 2008
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Konferensbidrag (refereegranskat)abstract
- Objectives: To study the diagnostic accuracy of the clinical examination of the Research Diagnostic Criteria (RDC) and of the dynamic and static pain tests for the recognition of temporomandibular disorder (TMD) pain. Methods: A blind examination, including all clinical tests needed for a RDC diagnosis of TMD pain, and the dynamic and static pain tests, was performed in 125 chronic TMD pain patients, 88 chronic dental pain patients, and 121 pain-free subjects. Allocation was based upon the results of an oral history and a dental examination. As indicators for diagnostic accuracy, sensitivity and specificity of the RDC examination and of the dynamic and static pain tests were compared to recommended levels of .70 and .90, respectively. Results: For the RDC examination, high sensitivity (.88), but lower specificity (.45-.71) was found. The specificity did not reach its recommended level. For the dynamic and static pain tests, specificity (.84-.91) and sensitivity (.65) did not differ from the recommended levels. Comparing the outcomes of the two examinations showed that the positive likelihood ratios of the dynamic and static pain tests were higher (p<.001), while the negative likelihood ratios of the RDC examination were lower (p<.01). Conclusion: For the confirmation of a suspected TMD origin of orofacial pain, it is better to rely on the dynamic and static pain tests. To rule out a TMD origin, more value should be attached to the RDC examination (no funding sources).
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| 3. |
- Visscher, Corinne, et al.
(författare)
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Accuracy of RDC/TMD examination and dynamic/static tests
- 2008
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Konferensbidrag (refereegranskat)abstract
- Objectives: To study the diagnostic accuracy of the clinical examination of the Research Diagnostic Criteria (RDC) and of the dynamic and static pain tests for the recognition of temporomandibular disorder (TMD) pain and to improve the RDC accuracy by 1) changing the myofascial pain cutoff of 3 painful muscle palpation sites, or 2)omitting unreliable palpation sites. Methods: In 4 European dental faculties, a blind examination was performed in 125 chronic TMD pain patients, 88 chronic dental pain patients, and 121 pain-free subjects. Allocation was based upon the results of an oral history and a dental examination. Results: Sensitivity and specificity of the RDC were .88 and 45-.71, respectively. Increasing the myofascial pain cutoff better met the recommended levels for specificity and sensitivity of .70 and .90, respectively. When unreliable muscle palpation sites (i.e., the intraoral and submandibular sites) were omitted, the accuracy of the RDC/TMD examination did not change. For the dynamic and static pain tests, sensitivity (.65) and specificity (.84-.91) did not differ significantly from the recommended levels. Conclusion: A suspected TMD origin of orofacial pain is best confirmed by pain on the dynamic or static tests, while it is better denied by a negative outcome of the RDC examination. The intraoral and submandibular palpation sites of the RDC examination do not contribute to its diagnostic accuracy and can better be omitted, while the cutoff for a myofascial pain diagnosis should be increased.
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