| 1. |
- Jones, Gregory T., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 2. |
- Lo Faro, Valeria, Postdoc, et al.
(författare)
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Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation
- 2024
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Ingår i: Cell Reports Medicine. - : Elsevier. - 2666-3791. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Primary open -angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta -analysis across 15 biobanks (of the Global Biobank Meta -analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multiancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene -enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis.
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| 3. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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| 4. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 5. |
- Kumar, Rakesh, et al.
(författare)
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Micro(nano)plastics pollution and human health : How plastics can induce carcinogenesis to humans?
- 2022
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 298, s. 134267-
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Tidskriftsartikel (refereegranskat)abstract
- Microplastics (MPs) and nanoplastics (NPs) are key indicators of the plasticine era, widely spread across different ecosystems. MPs and NPs become global stressors due to their inherent physicochemical characteristics and potential impact on ecosystems and humans. MPs and NPs have been exposed to humans via various pathways, such as tap water, bottled water, seafood, beverages, milk, fish, salts, fruits, and vegetables. This paper highlights MPs and NPs pathways to the food chains and how these plastic particles can cause risks to human health. MPs have been evident in vivo and vitro and have been at health risks, such as respiratory, immune, reproductive, and digestive systems. The present work emphasizes how various MPs and NPs, and associated toxic chemicals, such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), impact human health. Polystyrene (PS) and polyvinyl chloride (PVC) are common MPs and NPs, reported in human implants via ingestion, inhalation, and dermal exposure, which can cause carcinogenesis, according to Agency for Toxic Substances and Disease Registry (ATSDR) reports. Inhalation, ingestion, and dermal exposure-response cause genotoxicity, cell division and viability, cytotoxicity, oxidative stress induction, metabolism disruption, DNA damage, inflammation, and immunological responses in humans. Lastly, this review work concluded with
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| 6. |
- Singh, Mahesh Chand, et al.
(författare)
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GIS integrated RUSLE model-based soil loss estimation and watershed prioritization for land and water conservation aspects
- 2023
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Ingår i: Frontiers in Environmental Science. - : Frontiers Media S.A.. - 2296-665X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Land degradation has become one of the major threats throughout the globe, affecting about 2.6 billion people in more than 100 countries. The highest rate of land degradation is in Asia, followed by Africa and Europe. Climate change coupled with anthropogenic activities have accelerated the rate of land degradation in developing nations. In India, land degradation has affected about 105.48 million hectares. Thus, modeling and mapping soil loss, and assessing the vulnerability threat of the active erosional processes in a region are the major challenges from the land and water conservation aspects. The present study attempted rigorous modeling to estimate soil loss from the Banas Basin of Rajasthan state, India, using GIS-integrated Revised Universal Soil Loss Equation (RUSLE) equation. Priority ranking was computed for different watersheds in terms of the degree of soil loss from their catchments, so that appropriate conservation measures can be implemented. The total area of Banas basin (68,207.82 km2) was systematically separated into 25 watersheds ranging in area from 113.0 to 7626.8 km2. Rainfall dataset of Indian Meteorological Department for 30 years (1990–2020), FAO based Soil map for soil characterization, ALOS PALSAR digital elevation model for topographic assessment, and Sentinal-2 based land use and land cover map were integrated for modeling and mapping soil erosion/loss risk assessment. The total annual soil loss in the Banas basin was recorded as 21,766,048.8 tons. The areas under very low (0–1 t ha-1 year-1), low (1–5 t ha-1 year-1), medium (5–10 t ha-1 year-1), high (10–50 t ha-1 year-1) and extreme (>50 t ha-1 year-1) soil loss categories were recorded as 24.2, 66.8, 7.3, 0.9, and 0.7%, respectively, whereas the respective average annual soil loss values were obtained as 0.8, 3.0, 6.0, 23.1, and 52.0 t ha-1 year-1. The average annual soil loss among different watersheds was recorded in the range of 1.1–84.9 t ha-1 year-1, being highest (84.9 t ha-1 year-1) in WS18, followed by WS10 (38.4 t ha-1 year-1), SW25 (34.7 t ha-1 year-1) and WS23 (17.9 t ha-1 year-1), whereas it was lowest for WS8 (1.1 t ha-1 year-1). Thus, WS18 obtained the highest/top priority rank in terms of the average annual soil loss (84.9 t ha-1 year-1) to be considered as the first priority for land and water conservation planning and implementation. The quantitative results of this study would be useful for implementation of land and water conservation measures in the problematic areas of the Banas basin for controlling soil loss through water erosion.
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| 7. |
- Wärnberg Gerdin, Ludvig, et al.
(författare)
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Comparison of emergency department trauma triage performance of clinicians and clinical prediction models : a cohort study in India
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to evaluate and compare the abilities of clinicians and clinical prediction models to accurately triage emergency department (ED) trauma patients. We compared the decisions made by clinicians with the Revised Trauma Score (RTS), the Glasgow Coma Scale, Age and Systolic Blood Pressure (GAP) score, the Kampala Trauma Score (KTS) and the Gerdin et al model. Design Prospective cohort study. Setting Three hospitals in urban India. Participants In total, 7697 adult patients who presented to participating hospitals with a history of trauma were approached for enrolment. The final study sample included 5155 patients. The majority (4023, 78.0%) were male. Main outcome measure The patient outcome was mortality within 30 days of arrival at the participating hospital. A grid search was used to identify model cut-off values. Clinicians and categorised models were evaluated and compared using the area under the receiver operating characteristics curve (AUROCC) and net reclassification improvement in non-survivors (NRI+) and survivors (NRI-) separately. Results The differences in AUROCC between each categorised model and the clinicians were 0.016 (95% CI-0.014 to 0.045) for RTS, 0.019 (95% CI-0.007 to 0.058) for GAP, 0.054 (95% CI 0.033 to 0.077) for KTS and-0.007 (95% CI-0.035 to 0.03) for Gerdin et al. The NRI+ for each model were-0.235 (-0.37 to-0.116), 0.17 (-0.042 to 0.405), 0.55 (0.47 to 0.65) and 0.22 (0.11 to 0.717), respectively. The NRI-were 0.385 (0.348 to 0.4), -0.059 (-0.476 to-0.005),-0.162 (-0.18 to-0.146) and 0.039 (-0.229 to 0.06), respectively. Conclusion The findings of this study suggest that there are no substantial differences in discrimination and net reclassification improvement between clinicians and all four clinical prediction models when using 30-day mortality as the outcome of ED trauma triage in adult patients.
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