| 1. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 4. |
- Dengler, Juergen, et al.
(författare)
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GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands
- 2018
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Ingår i: Phytocoenologia. - : Schweizerbart. - 0340-269X. ; 48:3, s. 331-347
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Tidskriftsartikel (refereegranskat)abstract
- GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
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| 5. |
- Bartosiewicz, Laszlo, 1954-, et al.
(författare)
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Animal Exploitation in Medieval Hungary
- 2018
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Ingår i: The Economy of Medieval Hungary. - Leiden : Brill Academic Publishers. - 9789004310155 ; , s. 113-165
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Bokkapitel (refereegranskat)abstract
- During the last few years there has been an upswing in interest in animal stud-ies among medievalists. Historical research into medieval animal husbandry and the use of related products has intensified in terms of the analysis of docu-mentary (and to some extent, iconographic) sources, but the help of archae-ologists has also been enlisted. Eventually, the study of animal bone finds also began, although this type of inquiry is far better developed in the field of pre-historic archaeology: in the absence of written sources, prehistorians had to turn to less spectacular evidence, including animal remains. Archaeozoology is devoted to the identification, analysis and interpretation of animal remains from archaeological sites. Although the detailed analysis of written sources and animal iconography fall outside the scope of archaeozoology, familiarity with this process is indispensable for properly interpreting the archaeological traces of medieval animal exploitation.
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| 6. |
- Armstrong, Chelsey, et al.
(författare)
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Anthropological contributions to historical ecology : 50 questions, infinite prospects
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.
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| 7. |
- Heldbjerg, Henning, et al.
(författare)
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Contrasting population trends of common starlings (Sturnus vulgaris) across Europe
- 2019
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Ingår i: Ornis Fennica. - 0030-5685. ; 96:4, s. 153-168
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Tidskriftsartikel (refereegranskat)abstract
- The greatest loss of biodiversity in the EU has occurred on agricultural land. The Common Starling (Sturnus vulgaris) is one of the many numerous and widespread European farmland breeding bird species showing major population declines linked to European agricultural intensification. Here we present results based on monitoring data collected since 1975 in 24 countries to examine the influence of changing extent of grassland and cattle abundance (based on results of earlier studies showing the importance of lowland cattle grazed grassland for the species), wintering provenance and temperature on national breeding population trends of Starlings across Europe. Positive Starling population trends in Central-East Europe contrast with negative trends in North and West Europe. Based on this indicative approach, we found some support for the importance of cattle stock and no support for grassland, temperature or wintering provenance to explain Starling population trends in Europe. However, we acknowledge such a European-wide analysis may conceal regional differences in responses and suggest that currently accessible national land use data might be insufficient to describe the detailed current changes in animal husbandry and grassland management that may be responsible for changes in food availability and hence breeding Starling abundance and their differences across Europe. Reviewing results from local studies relating Starling population trends to local agricultural change offer contradictory results, suggesting complex interacting processes at work. We recommend combining national datasets on demography, land-use/agricultural practices and from autecological research to better explain the reasons for contrasting Starling trends across Europe, to enable us to predict how changing agriculture will affect Starlings and potentially suggest mitigation measures to restore local populations where possible.
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| 8. |
- Leffler, Jonatan, et al.
(författare)
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Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome
- 2017
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 9:1, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neutrophil extracellular traps (NETs) can stimulate thrombosis, and their degradation is decreased in several autoimmune disorders. It was recently reported that some patients with haemolytic uraemic syndrome (HUS) also fail to degrade NETs and that neutrophils from Shiga toxin-associated HUS are primed to form NETs. Method: We used a well-characterized cohort of 74 thrombotic microangiopathy (TMA) patients, with a subset also providing follow-up samples, and 112 age-matched controls to investigate NET degradation and serum nuclease activity in TMA before, during and after treatment. Results: We identified that in the cohort of TMA patients, 50% of patients with Shiga toxin-associated HUS displayed a decreased ability to degrade NETs. NET degradation correlated with serum nuclease activity, but not with autoantibodies against double-stranded DNA, which has been previously observed in some autoimmune disorders. Further, NET degradation negatively correlated with serum creatinine levels, suggesting that kidney function was negatively impacted by the low NET degradation ability. Conclusions: We revealed that decreased NET degradation is a common feature of Shiga toxin-associated HUS and that it is associated with decreased kidney function in these patients. It remains to be clarified whether improving NET degradation would be beneficial for the patient.
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| 9. |
- Oudin, Anna, et al.
(författare)
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The association between daily concentrations of air pollution and visits to a psychiatric emergency unit: a case-crossover study
- 2018
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Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Air pollution is one of the leading causes of mortality and morbidity worldwide. Experimental studies, and a few epidemiological studies, suggest that air pollution may cause acute exacerbation of psychiatric disorders, and even increase the rate of suicide attempts, but epidemiological studies on air pollution in association with psychiatric disorders are still few. Our aim was to investigate associations between daily fluctuations in air pollution concentrations and the daily number of visits to a psychiatric emergency unit. Methods: Data from Sahlgrenska University Hospital, Gothenburg, Sweden, on the daily number of visits to the Psychiatric emergency unit were combined with daily data on monitored concentrations of respirable particulate matter(PM10), ozone(O-3), nitrogen dioxides(NO2) and temperature between 1st July 2012 and 31st December 2016. We used a case-crossover design to analyze data with conditional Poisson regression models allowing for over-dispersion. We stratified data on season. Results: Visits increased with increasing PM10 levels during the warmer season (April to September) in both single-pollutant and two-pollutant models. For example, an increase of 3.6% (95% Confidence Interval, CI, 0.4-7.0%) was observed with a 10 mu g/m(3) increase in PM10 adjusted for NO2. In the three-pollutant models (adjusting for NO2 and O-3 simultaneously) the increase was 3.3% (95% CI, -0.2-6.9). There were no clear associations between the outcome and NO2, O-3, or PM10 during the colder season (October to March). Conclusions: Ambient air particle concentrations were associated with the number of visits to the Psychiatric emergency unit in the warm season. The results were only borderline statistically significant in the fully adjusted (three-pollutant) models in this small study. The observation could be interpreted as indicative of air pollution as either exacerbating an underlying psychiatric disorder, or increasing mental distress, even in areas with comparatively low levels of air pollution. In combination with the severe impact of psychiatric disorders and mental distress on society and individuals, our results are a strong warrant for future research in this area.
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| 10. |
- Rebbeck, Timothy R., et al.
(författare)
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Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
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