| 1. |
- Bellenguez, Celine, et al.
(författare)
-
Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:3, s. 141-328
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
|
|
| 2. |
- Craddock, Nick, et al.
(författare)
-
Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
-
Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
|
|
| 3. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
|
|
| 4. |
- De Alwis, Roger, et al.
(författare)
-
Size-based isolation and detection of renal carcinoma cells from whole blood
- 2022
-
Ingår i: Molecular and clinical oncology. - : Spandidos Publications. - 2049-9450 .- 2049-9469. ; 16:5
-
Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) is a tumour type with an indolent growth pattern and rather vague symptoms. The present study developed a platform for liquid biopsy of RCC based upon the isolation of circulating tumour cells (CTCs). Founded on the observation that RCC tumour cells are considerably larger than leucocytes, the present study employed a microfluidics-based system for isolation of RCC CTCs from whole blood. Using this system, it was revealed that 66% of spiked-in RCC tumour cells could be retrieved using this approach. Furthermore, it was demonstrated that these cells could be molecularly detected with digital PCR using RCC-specific genes down to one tumour cell, whilst avoiding detection in samples lacking tumour cells. Finally, subtype specific transcripts were identified to distinguish the different subtypes of RCC, which were then validated in patient tumours. The present study established a novel workflow for the isolation of RCC CTCs from whole blood, with the potential to detect these cells irrespective of subtype.
|
|
| 5. |
- Ekdahl, Anna-Lena, et al.
(författare)
-
Gemensamt fokus på förskolebarns taluppfattning och aritmetiska förmågor : Ett samverkansprojekt där teori och praktik flätas samman
- 2018
-
Konferensbidrag (refereegranskat)abstract
- I forskningsprojektet FASETT[1] flätas teori och praktik samman. Projektet syftar till att generera kunskap om barns tidiga taluppfattning, utifrån delvis andra perspektiv än de dominerande inom fältet, och se hur en pedagogisk verksamhet i samverkan med forskare kan bidra till barns utveckling av aritmetikfärdigheter.I projektet arbetade nio förskollärare och 65 femåringar på fem förskolenheter i ett tätt samarbete med en grupp forskare under en åttamånadersperiod. Deltagarna träffades kontinuerligt, diskuterade och fördjupade sig i aritmetiken med fokus på aktiviteter gällande de tio första talens del-del-helhetsrelationer. Aktiviteterna var till viss del välkända, men bearbetade utifrån tidigare forskningsresultat och variationsteorin (Neuman, 1987; Marton, 2015). Utgångspunkten och reflektionerna vid gruppträffarna var intervjuer av barnens olika sätt att uppfatta tal och lösa enklare aritmetikproblem samt lärarnas iscensättande av de planerade aktiviteterna. Genom att gemensamt diskutera de filmade aktiviteterna kunde aktiviteterna förfinas och förskollärarnas didaktik utvecklas för att möta barnens behov. Pågående analyser visar att designen av projektet möjliggjort för förskollärare och forskare att i kollaboration implementera ett alternativt teoretiskt underbyggt sätt att utveckla barns taluppfattning och förmåga att lösa enklare aritmetikproblem genom att exempelvis använda sig av fingrarna som redskap för att strukturera talrelationer och inte enbart räkna ’ett till ett’.Analysen av de barnintervjuer som gjordes innan aktiviteterna introduceras och de barnintervjuer som gjordes efter forskningsprojektets slut visar att förskollärarnas målorienterade processer med största sannolikhet haft effekter på barnens aritmetiska förmågor. De preliminära resultaten indikerar att valet av att fokusera på ett fåtal aktiviteter möjliggjorde för en djupare reflektion kring teoretiska antaganden och vad barn behöver få syn på för att lära sig om tal och talrelationer.[1] ”Förmågan Att Sinnligt Erfara de Tio första Talen som nödvändig grund för aritmetiska färdigheter”, finansierat av Vetenskapsrådet 2015-2018
|
|
| 6. |
- Elden, Helen, 1959, et al.
(författare)
-
Feeling old in a young body: Women’s experiences of living with severe consequences of an obstetric anal sphincter rupture: An interview study.
- 2014
-
Ingår i: Clinical Nursing Studies. - : Sciedu Press. - 2324-7940 .- 2324-7959. ; 3:1, s. 20-28
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The incidence of obstetric anal sphincter rupture (OASR) is increasing. It may cause anal incontinence and dyspareunia, leading to reduced quality of life and wellbeing. Qualitative studies are lacking. The aim was to describe experiences of living with ongoing severe consequences of an OASR 8 weeks after childbirth. Method: Twenty women with ongoing severe consequences of an OASR 8 weeks after delivery were interviewed using qualitative content analysis. Results: The experience of complications of an OASR is described in the overall theme ”Feeling old in a young body” and four categories: The body as injured; isolation; inability to function sexually, and anxiety for the future. Participants described how the consequences of OASR totally occupied their lives, making them feel old in a young body. They told of repercussions for their physical, psychological, sexual and social lives; how it affected their roles of mothers and partners, making them fear future childbirths. Diet, use of medicines, coal filters in incontinence pads, timing of toilet visits, use of the environment and mobile phones to conceal flatus and/or feces were strategies participants described. Conclusions: This study can contribute to increased understanding of how women can be affected by an OASR, and may enable healthcare personnel and authorities to meet their needs and organize care so that adequate support is available. It would also be beneficial if the women’s physical strategies were integrated into the information provided by health caregivers involved in follow-up. However, more research in this area is warranted.
|
|
| 7. |
- Evangelou, Evangelos, et al.
(författare)
-
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
-
Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
|
|
| 8. |
- Granholm, Ann-Helen, et al.
(författare)
-
Estimating vertical canopy cover using dense image-based point cloud data in four vegetation types in southern Sweden
- 2017
-
Ingår i: International Journal of Remote Sensing. - : Informa UK Limited. - 0143-1161 .- 1366-5901. ; 38, s. 1820-1838
-
Tidskriftsartikel (refereegranskat)abstract
- This study had the aim of investigating the utility of image-based point cloud data for estimation of vertical canopy cover (VCC). An accurate measure of VCC based on photogrammetric matching of aerial images would aid in vegetation mapping, especially in areas where aerial imagery is acquired regularly. The test area is located in southern Sweden and was divided into four vegetation types with sparse to dense tree cover: unmanaged coniferous forest; pasture areas with deciduous tree cover; wetland; and managed coniferous forest. Aerial imagery with a ground sample distance of 0.24 m was photogrammetrically matched to produce dense image-based point cloud data. Two different image matching software solutions were used and compared: MATCH-T DSM by Trimble and SURE by nFrames. The image-based point clouds were normalized using a digital terrain model derived from airborne laser scanner (ALS) data. The canopy cover metric vegetation ratio was derived from the image-based point clouds, as well as from raster-based canopy height models (CHMs) derived from the point clouds. Regression analysis was applied with vegetation ratio derived from near nadir ALS data as the dependent variable and metrics derived from image-based point cloud data as the independent variables. Among the different vegetation types, vegetation ratio derived from the image-based point cloud data generated by using MATCH-T resulted in relative root mean square errors (rRMSE) of VCC ranging from 6.1% to 29.3%. Vegetation ratio based on point clouds from SURE resulted in rRMSEs ranging from 7.3% to 37.9%. Use of the vegetation ratio based on CHMs generated from the image-based point clouds resulted in similar, yet slightly higher values of rRMSE.
|
|
| 9. |
- Granholm, Ann-Helen, et al.
(författare)
-
Estimating vertical canopy cover with dense point cloud data from matching of digital aerial photos
- 2015
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This study aims to explore the use of dense point clouds from matching of aerial photos for estimation of vertical canopy cover (VCC), defined as the proportion of the forest floor covered by the vertical projection of the tree crowns. VCC is commonly estimated using vegetation ratio (VR) derived from airborne laser scanner (ALS) data. A reliable measure of VCC from matching aerial photos would aid in vegetation mapping and reduce the need for repeated ALS data acquisition. The test area is located in southern Sweden and covers a variety of vegetation types. In total 367 sample plots were placed in parts of the study area representing VCC ranging from 0 % up to close to 100 %. ALS data with a density of 20 returns per m2 was used for calculating the VR as the proportion of first returns above a threshold. Aerial imagery with a ground sample distance of 0.25 m was matched to produce dense point cloud data, which was used to derive digital surface models (DSMs) with grid size from 0.25 m up to 2.0 m. Local maxima (LM) detection was applied to the DSMs with search windows of 0.5 m size up to 2.0 m. The heights of the LM were normalized using a digital elevation model (DEM) derived from ALS data. Regression analysis was applied with the VR as dependent variable and the sum of the height of LM within sample plots as independent variable. Results from linear regression using heights of LM detected in a DSM of 0.25 m resolution with a 0.5 m search window gave an root mean square error (RMSE) of 5.5 % and relative RMSE (rRMSE) of 9.3 % in forest on rocky outcrops and boulders, while wooded pasture gave RMSE = 6.3 % and rRMSE = 19 %.
|
|
| 10. |
- Hansson, Jennifer, et al.
(författare)
-
Overexpression of functional SLC6A3 in clear cell renal cell carcinoma
- 2017
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:8, s. 2105-2115
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Renal cell carcinoma (RCC) is derived from a tissue with a remarkable capacity for vectorial transport. We therefore performed an unbiased exploration of transporter proteins in normal kidney and kidney cancer in order to discover novel clinical targets.EXPERIMENTAL DESIGN: Using the TCGA database we investigated differences in membrane transporter expression in ccRCC and normal kidney. We identified the dopamine transporter SLC6A3 as a specific biomarker for ccRCC. To investigate the functionality of SLC6A3 we used a [3H]-dopamine uptake assay on ccRCC cells. We further explored the effect of HIF proteins on SLC6A3 expression by introducing siRNA in ccRCC cells and by hypoxic treatment of non-malignant cells.RESULTS: We show that ccRCC express very high transcript levels of SLC6A3 in contrast to normal kidney tissue and other tumor types, which do not express appreciable levels of this transporter. Importantly, we demonstrate that the elevated expression of SLC6A3 in ccRCC cells is associated with specific uptake of dopamine. By targeting the expression of HIF-1α and HIF-2α we could show that SLC6A3 expression is primarily influenced by HIF-2α, and that hypoxia can induce SLC6A3 expression in normal renal cells.CONCLUSIONS: We conclude that the dopamine transporter SLC6A3 constitute a novel biomarker that is highly specific for ccRCC. We further postulate that the protein can be exploited for diagnostic or therapeutic purposes for detection or treatment of ccRCC.
|
|
