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- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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| 2. |
- Gallo, Valentina, et al.
(författare)
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Smoking and risk for amyotrophic lateral sclerosis : analysis of the EPIC cohort
- 2009
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Ingår i: Annals of Neurology. - New York : J. Wiley & Sons. - 0364-5134 .- 1531-8249. ; 65:4, s. 378-385
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. Methods: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. Results: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. Interpretation: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure.
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| 3. |
- Agner, Tove, et al.
(författare)
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Contact sensitisation in hand eczema patients-relation to subdiagnosis, severity and quality of life: a multi-centre study
- 2009
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Ingår i: Contact Dermatitis. - 0105-1873. ; 61:5, s. 291-296
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Tidskriftsartikel (refereegranskat)abstract
- Background Contact sensitisation has been identified as a factor associated with poor prognosis for patients with hand eczema. Objectives To study implications of contact sensitisation with respect to severity, quality of life (QoL) and subdiagnosis of hand eczema. Methods The study was performed as a multi-centre, cross-sectional study from 10 European clinics. All patients were patch tested, and severity of hand eczema assessed by Hand Eczema Severity Index. A multi-variate analysis was performed to explore which factors influenced severity, QoL and sick leave. Results A total 416 patients were included, and 63% had contact sensitisation to one or more of the tested allergens. More women (66%) than men (51%) were sensitized. No significant association was found between sensitisation to specific allergens, disease severity, QoL or diagnostic subgroups. High age, male sex, atopic eczema and presence of contact sensitisation were independent risk factors for increased severity as measured by Hand Eczema Severity Index. Furthermore, the severity of hand eczema increased by the number of contact sensitisations detected (P = 0.023). High age and personal history of atopic eczema were independent risk factors for low QoL, as measured by Dermatology Life Quality Index, and atopic eczema as well as allergic contact dermatitis as subdiagnosis was associated with increased sick leave. Conclusion Diagnostic subgroups were not found to be related to specific allergens. Contact sensitisation was found to be a risk factor for increased severity of hand eczema, as did high age, male sex and atopic eczema.
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| 4. |
- Agner, Tove, et al.
(författare)
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Hand eczema severity and quality of life: a cross-sectional, multicentre study of hand eczema patients
- 2008
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 59:1, s. 43-47
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Hand eczema is a chronic disease with negative impact on quality of life (QoL). In this study, QoL in hand eczema patients is assessed and related to age, sex, severity, and diagnostic subgroups. Methods: A total of 416 patients with hand eczema from 10 European patch test clinics participated in the study. Data on QoL were obtained from a self-administered questionnaire using the Dermatology Life Quality Index (DLQI). Severity was assessed by a scoring system (Hand Eczema Severity Index, HECSI) as well as frequency of eruptions and sick leave due to hand eczema. Results: No significant difference was found between males and females with respect to QoL [DLQI median values and 25/75 percentiles for males and females being 7.0 (3-14) and 8.0 (3-13), respectively], although males were more severely affected than females (P < 0.025). A significant positive correlation was found for hand eczema severity and age (P < 0.001), while no significant correlation was found for QoL and age. QoL was found increasingly reduced when sick leave was getting higher (P < 0.001). A statistically significant correlation between QoL (as measured by DLQI) and hand eczema severity as measured by HECSI was found (P < 0.001). No significant difference in QoL was found between diagnostic subgroups. Conclusions: QoL was found markedly negatively affected in hand eczema patients and was significantly correlated to disease severity. No significant difference in QoL was found between males and females, in spite of significantly more severe eczema in males, indicating that QoL in female patients is more easily affected.
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| 6. |
- Wejse, Christian, et al.
(författare)
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Vitamin D as Supplementary Treatment for Tuberculosis A Double-blind, Randomized, Placebo-controlled Trial
- 2009
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 179:9, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Rationale Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. Objectives: To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. Methods: We conducted a randomized, double-blind, place-bocontrolled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. Measurements and Main Results: The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at I year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Conclusions: Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).
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