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- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 5. |
- Bhatta, L, et al.
(författare)
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Bone mineral density and risk of cardiovascular disease in men and women: the HUNT study
- 2021
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 36:11, s. 1169-1177
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Tidskriftsartikel (refereegranskat)abstract
- The association between bone mineral density (BMD) and cardiovascular disease (CVD) is not fully understood. We evaluated BMD as a risk factor for cardiovascular disease and specifically atrial fibrillation (AF), acute myocardial infarction (AMI), ischemic (IS) and hemorrhagic stroke (HS) and heart failure (HF) in men and women. This prospective population cohort utilized data on 22 857 adults from the second and third surveys of the HUNT Study in Norway free from CVD at baseline. BMD was measured using single and dual-energy X-ray absorptiometry in the non-dominant distal forearm and T-score was calculated. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated from adjusted cox proportional hazards models. The analyses were sex-stratified, and models were adjusted for age, age-squared, BMI, physical activity, smoking status, alcohol use, and education level. Additionally, in women, we adjusted for estrogen use and postmenopause. During a mean follow-up of 13.6 ± 5.7 years, 2 928 individuals (12.8%) developed fatal or non-fatal CVD, 1 020 AF (4.5%), 1 172 AMI (5.1%), 1 389 IS (6.1%), 264 HS (1.1%), and 464 HF (2.0%). For every 1 unit decrease in BMD T-score the HR for any CVD was 1.01 (95% CI 0.98 to 1.04) in women and 0.99 (95% CI 0.94 to 1.03) in men. Point estimates for the four cardiovascular outcomes ranged from slightly protective (HR 0.95 for AF in men) to slightly deleterious (HR 1.12 for HS in men). We found no evidence of association of lower distal forearm BMD with CVD, AF, AMI, IS, HS, and HF.
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| 7. |
- Biurrun, Idoia, et al.
(författare)
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Benchmarking plant diversity of Palaearctic grasslands and other open habitats
- 2021
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Ingår i: Journal of Vegetation Science. - Oxford : John Wiley & Sons. - 1100-9233 .- 1654-1103. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- Journal of Vegetation Science published by John Wiley & Sons Ltd on behalf of International Association for Vegetation Science.Aims: Understanding fine-grain diversity patterns across large spatial extents is fundamental for macroecological research and biodiversity conservation. Using the GrassPlot database, we provide benchmarks of fine-grain richness values of Palaearctic open habitats for vascular plants, bryophytes, lichens and complete vegetation (i.e., the sum of the former three groups). Location: Palaearctic biogeographic realm. Methods: We used 126,524 plots of eight standard grain sizes from the GrassPlot database: 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 and 1,000 m2 and calculated the mean richness and standard deviations, as well as maximum, minimum, median, and first and third quartiles for each combination of grain size, taxonomic group, biome, region, vegetation type and phytosociological class. Results: Patterns of plant diversity in vegetation types and biomes differ across grain sizes and taxonomic groups. Overall, secondary (mostly semi-natural) grasslands and natural grasslands are the richest vegetation type. The open-access file ”GrassPlot Diversity Benchmarks” and the web tool “GrassPlot Diversity Explorer” are now available online (https://edgg.org/databases/GrasslandDiversityExplorer) and provide more insights into species richness patterns in the Palaearctic open habitats. Conclusions: The GrassPlot Diversity Benchmarks provide high-quality data on species richness in open habitat types across the Palaearctic. These benchmark data can be used in vegetation ecology, macroecology, biodiversity conservation and data quality checking. While the amount of data in the underlying GrassPlot database and their spatial coverage are smaller than in other extensive vegetation-plot databases, species recordings in GrassPlot are on average more complete, making it a valuable complementary data source in macroecology. © 2021 The Authors.
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| 9. |
- Deuba, K, et al.
(författare)
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Risk of HIV infection among men having sex with men in Kathmandu Valley, Nepal
- 2014
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Ingår i: Asia-Pacific journal of public health. - : SAGE Publications. - 1941-2479 .- 1010-5395. ; 26:2, s. 126-137
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Tidskriftsartikel (refereegranskat)abstract
- Despite extensive distribution of free condoms and lubricants to prevent HIV transmission among men having sex with men (MSM) in Nepal, the prevalence of HIV and risky sexual behaviors remain high. The influence of individual-level, social-capital, and social-structural factors on HIV risk has been insufficiently explored in MSM. The authors assessed association of these factors with HIV risk among 150 MSM enrolled using snowball sampling in the Kathmandu Valley. HIV risk was calculated on the basis of number and type of sexual partners and condom use during anal sex. Multivariate analysis showed a high risk of HIV infection was significantly associated with being involved in sex work, having no knowledge of male sexually transmitted infection (STI) symptoms, and having a history of STI symptoms. HIV prevention could be made more effective by targeting MSM who are involved in sex work and by improving their knowledge of male STI symptoms and early diagnosis and treatment.
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- Korologou-Linden, R, et al.
(författare)
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The causes and consequences of Alzheimer's disease: phenome-wide evidence from Mendelian randomization
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4726-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) has no proven causal and modifiable risk factors, or effective interventions. We report a phenome-wide association study (PheWAS) of genetic liability for AD in 334,968 participants of the UK Biobank study, stratified by age. We also examined the effects of AD genetic liability on previously implicated risk factors. We replicated these analyses in the HUNT study. PheWAS hits and previously implicated risk factors were followed up in a Mendelian randomization (MR) framework to identify the causal effect of each risk factor on AD risk. A higher genetic liability for AD was associated with medical history and cognitive, lifestyle, physical and blood-based measures as early as 39 years of age. These effects were largely driven by the APOE gene. The follow-up MR analyses were primarily null, implying that most of these associations are likely to be a consequence of prodromal disease or selection bias, rather than the risk factor causing the disease.
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