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- Wang, Thomas J, et al.
(author)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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In: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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| 2. |
- Linton, Steven J., et al.
(author)
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Development of a short form of the Örebro musculoskeletal pain screening questionnaire
- 2011
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In: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 36:22, s. 1891-1895
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Journal article (peer-reviewed)abstract
- Study Design: A longitudinal design where the questionnaire was completed at a pre test and predictive ability evaluated with a one-year follow-up. A second sample was employed to provide a replication.Objective: The aim of the study was to validate a short form of the Örebro Musculoskeletal Pain ScreeningQuestionnaire: Summary of Background Data. Several studies demonstrate the research and clinical utility of the Örebro Musculoskeletal Pain Screening Questionnaire. Calls have been made for a shorter form that requires less time in administering.Methods: The short version was constructed by taking two items from each of the five factors shown to have predictive power. It was then tested against the long form in two samples of people with musculoskeletal pain where one reflects an occupational health care population (N = 324) and the other a primary care population (N = 183) thus providing a built-in replication. All participants completed the Örebro Musculoskeletal Pain Screening Questionnaire and were then followed over the course of a year to evaluate disability as measured by sick leave.Results: The correlation between the short and long forms was.91. The ROC curve was nearly identical for the long and short versions of the questionnaire (e.g. primary care sample:.84 versus.81; occupational sample:.72 versus.70). Of those who developed disability, a cutoff of 50 on the short version identified 85% in the occupational and 83% in the primary care samples which was nearly as good as the full version (92% respectively 83%).Conclusions: The short form of the Örebro Musculoskeletal Pain Screening Questionnaire is appropriate for clinical and research purposes since it is nearly as accurate as the longer version.
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| 3. |
- Linton, Steven J., et al.
(author)
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The role of depression and catastrophizing in musculoskeletal pain
- 2011
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In: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 15:4, s. 416-422
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Journal article (peer-reviewed)abstract
- Many patients with musculoskeletal pain also suffer from a depressed mood. Catastrophizing is one process that may link depression and pain since it is a key concept in models of both problems. Earlier research has suggested that catastrophizing measures something above and beyond depression. This study tests the idea that if depressed mood and catastrophizing are separate entities then when one is absent the other should still contribute to poor outcome, and, when both are present there should be an additional adverse effect. To this end, a prospective design, with a built-in replication from two clinical samples of patients with sub-acute pain (one from Sweden, N=373; one from Australasia, N=259), was employed. Participants were classified as to having high/low scores on measures of depression and catastrophizing. Subsequently, these classifications were studied in relation to outcome variables cross-sectionally and at follow-up. Results showed a small to moderate correlation between catastrophizing and depression and that there are individuals with one, but not the other problem. Further, having one or the other of the entities was associated with current pain problems and outcome, while having both increased the associations substantially. The replication showed very similar results Our data demonstrate that pain catastrophizing and heightened depressed mood have an additive and adverse effect on the impact of pain, relative to either alone. It suggests that each should be assessed in the clinic and that future research should focus on treatments specifically designed to tackle both depressed mood and catastrophizing.
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