| 1. |
- Skibola, Christine F, et al.
(författare)
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Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 95:4, s. 462-471
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
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| 4. |
- Andel, Ross, et al.
(författare)
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Work-Related Stress May Increase the Risk of Vascular Dementia
- 2012
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 60:1, s. 60-67
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine job control, job demands, social support at work, and job strain (ratio of demands to control) in relation to risk of any dementia, Alzheimer's disease (AD), and vascular dementia (VaD). DESIGN: Cohort study. SETTING: The population-based Study of Dementia in Swedish Twins. PARTICIPANTS: Two hundred fifty-seven people with dementia (167 AD, 46 VaD) and 9,849 without. MEASUREMENTS: Dementia diagnoses were based on telephone screening for cognitive impairment followed by in-person clinical examination. An established job exposure matrix was matched to main occupation categories to measure work characteristics. RESULTS: In generalized estimating equations (adjusted for the inclusion of complete twin pairs), lower job control was associated with greater risk of any dementia (odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.04-1.31) and VaD specifically (OR = 1.39, 95% CI = 1.07-1.81). Lower social support at work was associated with greater risk of dementia (OR = 1.15, 95% CI = 1.03-1.28), AD (OR = 1.14, 95% CI = 1.00-1.31), and VaD (OR = 1.28, 95% CI = 1.02-1.60). Greater job strain was associated with greater risk of VaD only (OR = 1.28, 95% CI = 1.02-1.60), especially in combination with low social support (OR = 1.35, 95% CI = 1.11-1.64). Age, sex, and education were controlled for. Work complexity, manual work, and vascular disease did not explain the results. No differences in work-related stress scores were observed in the 54 twin pairs discordant for dementia, although only two pairs included a twin with VaD. CONCLUSION: Work-related stress, including low job control and low social support at work, may increase the risk of dementia, particularly VaD. Modification to work environment, including attention to social context and provision of meaningful roles for employees, may contribute to efforts to promote cognitive health.
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| 6. |
- Hughes, Tiffany F, et al.
(författare)
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Midlife fruit and vegetable consumption and risk of dementia in later life in Swedish twins.
- 2010
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Ingår i: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. - 1545-7214 .- 1064-7481. ; 18:5, s. 413-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Diet may be associated with risk of dementia and Alzheimer disease (AD). The authors examined the association between fruit and vegetable consumption in midlife and risk for all types of dementia and AD. METHODS: Participants were 3,779 members of the Swedish Twin Registry who completed a diet questionnaire approximately 30 years before cognitive screening and full clinical evaluation for dementia as part of the study of dementia in Swedish Twins (HARMONY) study. Among the participants, 355 twins were diagnosed with dementia. Among these, 81 twin pairs were discordant for dementia (50 discordant for AD). Data were analyzed with logistic regression for the entire sample using generalized estimating equations to adjust for relatedness of twins and with conditional logistic regression for the co-twin control design. RESULTS: In fully adjusted models, a medium or great proportion of fruits and vegetables in the diet, compared with no or small, was associated with a decreased risk of dementia and AD. This effect was observed among women and those with angina. Similar, but nonsignificant, odds ratios were found in the co-twin control analyses. CONCLUSION: The findings suggest that higher fruit and vegetable consumption may reduce the risk of dementia, especially among women and those with angina pectoris in midlife.
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| 7. |
- Knox-Brown, Ben, et al.
(författare)
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Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study : a multinational cross-sectional study
- 2023
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:1, s. E69-E82
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters.Methods: The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF25-75) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 mu g salbutamol) and post-bronchodilator (ie, after administration of 200 mu g salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis.Findings: 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV3/FVC ratio and 25 961 participants for FEF25-75. Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF25-75, and for FEV 3/FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV 3/FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF25-75, except for increasing age, which was associated with reduced odds of small airways obstruction.Interpretation: Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline.
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| 8. |
- Knox-Brown, Ben, et al.
(författare)
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The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life : results from the Burden of Obstructive Lung Disease (BOLD) study
- 2023
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Ingår i: Respiratory Research. - : BioMed Central (BMC). - 1465-9921 .- 1465-993X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSpirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown.MethodsUsing data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN).ResultsAlmost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease.ConclusionSpirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.
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| 9. |
- Lyons, Oliver, et al.
(författare)
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Mutations in EPHB4 cause human venous valve aplasia
- 2021
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Ingår i: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:18
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Tidskriftsartikel (refereegranskat)abstract
- Venous valve (VV) failure causes chronic venous insufficiency, but the molecular regulation of valve development is poorly understood. A primary lymphatic anomaly, caused by mutations in the receptor tyrosine kinase EPHB4, was recently described, with these patients also presenting with venous insufficiency. Whether the venous anomalies are the result of an effect on VVs is not known. VV formation requires complex "organization" of valve-forming endothelial cells, including their reorientation perpendicular to the direction of blood flow. Using quantitative ultrasound, we identified substantial VV aplasia and deep venous reflux in patients with mutations in EPHB4. We used a GFP reporter in mice to study expression of its ligand, ephrinB2, and analyzed developmental phenotypes after conditional deletion of floxed Ephb4 and Efnb2 alleles. EphB4 and ephrinB2 expression patterns were dynamically regulated around organizing valve-forming cells. Efnb2 deletion disrupted the normal endothelial expression patterns of the gap junction proteins connexin37 and connexin43 (both required for normal valve development) around reorientating valve-forming cells and produced deficient valve-forming cell elongation, reorientation, polarity, and proliferation. Ephb4 was also required for valve-forming cell organization and subsequent growth of the valve leaflets. These results uncover a potentially novel cause of primary human VV aplasia.
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| 10. |
- Oliver, Tom H, et al.
(författare)
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Overcoming undesirable resilience in the global food system
- 2018
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Ingår i: Global Sustainability. - : Cambridge University Press (CUP). - 2059-4798. ; 1:e9, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Our current global food system – from food production to consumption, including manufacture, packaging, transport, retail and associated businesses – is responsible for extensive negative social and environmental impacts which threaten the long-term well-being of society. This has led to increasing calls from science–policy organizations for major reform and transformation of the global food system. However, our knowledge regarding food system transformations is fragmented and this is hindering the development of co-ordinated solutions. Here, we collate recent research across several academic disciplines and sectors in order to better understand the mechanisms that ‘lock-in’ food systems in unsustainable states.
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