| 1. |
- Palmer, Nicholette D, et al.
(författare)
-
A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
-
Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
-
Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
|
|
| 2. |
- Jakola, Asgeir Store, et al.
(författare)
-
The impact of resection in IDH-mutant WHO grade 2 gliomas: a retrospective population-based parallel cohort study.
- 2022
-
Ingår i: Journal of neurosurgery. - 1933-0693. ; 137:5
-
Tidskriftsartikel (refereegranskat)abstract
- IDH-mutant diffuse low-grade gliomas (dLGGs; WHO grade 2) are often considered to have a more indolent course. In particular, in patients with 1p19q codeleted oligodendrogliomas, survival can be very long. Therefore, extended follow-up in clinical studies of IDH-mutant dLGG is needed. The authors' primary aim was to determine results after a minimum 10-year follow-up in two hospitals advocating different surgical policies. In one center early resection was favored; in the other center an early biopsy and wait-and-scan approach was the dominant management. In addition, the authors present survival and health-related quality of life (HRQOL) in stratified groups of patients with IDH-mutant astrocytoma and oligodendroglioma.The authors conducted a retrospective, population-based, parallel cohort study with extended long-term follow-up. The inclusion criteria were histopathological diagnosis of IDH-mutant supratentorial dLGG from 1998 through 2009 in patients aged 18 years or older. Follow-up ended January 1, 2021; therefore, all patients had primary surgery more than 10 years earlier. In region A, a biopsy and wait-and-scan approach was favored, while early resections were advocated in region B. Regional referral practice ensured population-based data, since referral to respective centers was based strictly on the patient's residential address. Previous data from EQ-5D-3L, European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, and EORTC BN20 questionnaires were reanalyzed with respect to the current selection of IDH-mutant dLGG and to molecular subgroups. The prespecified primary endpoint was long-term regional comparison of overall survival. Secondarily, between-group differences in long-term HRQOL measures were explored.Forty-eight patients from region A and 56 patients from region B were included. Early resection was performed in 17 patients (35.4%) from region A compared with 53 patients (94.6%) from region B (p < 0.001). Characteristics at baseline were otherwise similar between cohorts. Overall survival was 7.5 years (95% CI 4.1-10.8) in region A compared with 14.6 years (95% CI 11.5-17.7) in region B (p = 0.04). When stratified according to molecular subgroups, there was only a statistically significant survival benefit in favor of early resection for patients with astrocytomas. The were no apparent differences in the different HRQOL measures between cohorts.In an extended follow-up of patients with IDH-mutant dLGGs, early resection was associated with a sustained and clinically relevant survival benefit. The survival benefit was not counteracted by any detectable reduction in HRQOL.
|
|
| 3. |
|
|
| 4. |
- Voight, Benjamin F., et al.
(författare)
-
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
-
Tidskriftsartikel (refereegranskat)abstract
- By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
|
|
| 5. |
- Aarstad, Olav, et al.
(författare)
-
Mechanical properties of composite hydrogels of alginate and cellulose nanofibrils
- 2017
-
Ingår i: Polymers. - : MDPI AG. - 2073-4360. ; 9:8
-
Tidskriftsartikel (refereegranskat)abstract
- Alginate and cellulose nanofibrils (CNF) are attractive materials for tissue engineering and regenerative medicine. CNF gels are generally weaker and more brittle than alginate gels, while alginate gels are elastic and have high rupture strength. Alginate properties depend on their guluronan and mannuronan content and their sequence pattern and molecular weight. Likewise, CNF exists in various qualities with properties depending on, e.g., morphology and charge density. In this study combinations of three types of alginate with different composition and two types of CNF with different charge and degree of fibrillation have been studied. Assessments of the composite gels revealed that attractive properties like high rupture strength, high compressibility, high gel rigidity at small deformations (Young’s modulus), and low syneresis was obtained compared to the pure gels. The effects varied with relative amounts of CNF and alginate, alginate type, and CNF quality. The largest effects were obtained by combining oxidized CNF with the alginates. Hence, by combining the two biopolymers in composite gels, it is possible to tune the rupture strength, Young’s modulus, syneresis, as well as stability in physiological saline solution, which are all important properties for the use as scaffolds in tissue engineering.
|
|
| 6. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 7. |
- Billaud Feragen, Kristin, et al.
(författare)
-
Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 10. Parental perceptions of appearance and treatment outcomes in their 5-year-old child
- 2017
-
Ingår i: Journal of Plastic Surgery and Hand Surgery. - : TAYLOR & FRANCIS LTD. - 2000-656X .- 2000-6764. ; 51:1, s. 81-87
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aim: Few studies have explored childrens emotional and behavioural reactions to cleft surgery and treatment-related stress. The objective was to investigate parents evaluations of appearance and treatment outcomes in their 5-year-old child with unilateral cleft lip and palate (UCLP), and their perceptions of how their child was coping with treatment, comparing this information with recorded postsurgical complications.Design: Three parallel group randomised clinical trials were undertaken as an international multicentre study by 10 cleft teams in five countries: Denmark, Finland, Sweden, Norway, and the UK.Methods: Three different surgical procedures for primary palatal repair were tested against a common procedure in the total cohort of 448 children born with a non-syndromic UCLP. A total of 356 parents completed the Scandcleft Parent Questionnaire, and 346 parents completed the Cleft Evaluation Profile.Results: The results indicated that the majority of parents were satisfied with cleft-related features of their childs appearance. Further, most children coped well with treatment according to their parents. Nevertheless, 17.5% of the children showed minor or short-term reactions after treatment experiences, and 2% had major or lasting difficulties. There were no significant relationships between parent perceptions of treatment-related problems and the occurrence of post-surgical medical complications.Conclusions: Most parents reported satisfaction with their childs appearance. However, treatment-related problems were described in some children, urging cleft centres to be aware of potential negative emotional and behavioural reactions to treatment in some young children, with a view to preventing the development of more severe treatment-related anxiety.
|
|
| 8. |
- Birney, Ewan, et al.
(författare)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
|
|
| 9. |
- Calvert, Clara, et al.
(författare)
-
Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries
- 2023
-
Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7:4, s. 529-544
-
Tidskriftsartikel (refereegranskat)abstract
- Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
|
|
| 10. |
- Do, Ron, et al.
(författare)
-
Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
-
Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
|
|
| 11. |
- Eising, Stefanie, et al.
(författare)
-
Type 1 diabetes risk analysis on dried blood spot samples from population-based newborns: design and feasibility of an unselected case-control study
- 2007
-
Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 21:6, s. 507-517
-
Tidskriftsartikel (refereegranskat)abstract
- Development of type 1 diabetes mellitus (T1D) may be triggered pre- or perinatally by multiple factors. Identifying new predisposing T1D markers or combinations of markers in a large, well-characterised case-control collection may be important for future T1D prevention. The present work describes the design and feasibility of a large and unselected case-control study, which will define and evaluate prediction criteria for T1D at the time of birth. Danish registries (Biological Specimen Bank for Neonatal Screening, and the National Discharge Registry) made it possible to identify and collect dried blood spots (DBS) from newborns who later developed T1D (cases) born 1981-2002. DBS samples from 2086 cases and two matching control subjects per case were analysed for genetic and immune factors that are associated with T1D: (a) candidate genes (HLA, INS and CTLA4), (b) cytokines and inflammatory markers, (c) islet auto-antibodies (GAD65A, IA-2A). The objective of the study was to define reliable prediction tools for T1D using samples available at the time of birth. In a unique approach, the study linked a large unselected and population-based sample resource to well-ascertained clinical databases and advanced technology. It combined genetic, immunological and demographic data to develop prediction algorithms. It also provided a resource for future studies in which new genetic markers can be included as they are identified.
|
|
| 12. |
- Feragen, Kristin, Billaud, et al.
(författare)
-
Scandcleft randomised trials of primary surgery for unilateral cleft lip and Palate: 9. Parental report of social and emotional experiences related to their 5-year-old child's cleft diagnosis
- 2017
-
Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 73-80
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aim:Parents of children with a cleft lip and palate may be emotionally affected by the child’s diagnosis. Their experiences and perceptions are important when evaluating the complexity of satisfactory treatment outcomes. The objective was to examine parents’ social and emotional experiences related to their child’s cleft diagnosis, and their perceptions of the child’s adjustment to living with a visible difference. Design:International multicentre study by 10 cleft teams in five countries: Denmark, Finland, Sweden, Norway, and the UK. Methods:A cohort of 448 children born with a non-syndromic UCLP were included. A total of 356 parents completed the Scandcleft Parent Questionnaire. Results:The majority of parents experienced practical and emotional support from family, friends, and health professionals. Nevertheless, parents had to cope with other people’s reactions to the cleft, experiences that were described as ranging from hurtful to neutral and/or positive. According to parents, 39% of the children had experienced cleft-related comments and/or teasing. More than half of the parents reported specific worries related to their child’s future. Conclusion:While the majority of the parents experienced positive support and coped well with the child’s diagnosis, some parents were at risk for psychological and emotional challenges that should be identified by the cleft team. To optimise outcomes and the child’s adjustment, these parents should be offered psychological support when necessary. Trial registration:ISRCTN29932826. [ABSTRACT FROM AUTHOR]
|
|
| 13. |
- Fjelldal, Per Gunnar, et al.
(författare)
-
Exogenous growth hormone (GH) increases dimension and reduces strength of vertebrae in Atlantic salmon (Salmo salar)
- 2024
-
Ingår i: AQUACULTURE. - 0044-8486 .- 1873-5622. ; 589
-
Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) administration increases bone strength in rats, mainly through alterations of the dimensional proportions of vertebrae. However, similar knowledge is lacking in other clades. In order to pursue this, Atlantic salmon were fed diets with high or low vitamin C and E and administered a slow -release implant of bovine GH. While neither the diets or the GH treatment affected growth, GH reduced condition factor and carcass -somatic index, and increased the hepatosomatic and visceral -somatic indexes. GH had an impact on the dimensional proportions of the vertebrae and increased the relative dorso-ventral and lateral vertebra diameters. Moreover, GH decreased the mechanical strength of the vertebra, both with (modulus of elasticity, failure point) and without (stiffness) normalizing the mechanical data for the dimensions of the vertebrae. Diet did not impact on the vertebra morphometry or mechanical strength. RNA-seq of vertebra centra show that several genes associated with bone growth and remodelling were affected by GH, while there was an interactive effect between diet vitamin level and GH on several genes associated with lipid metabolism. The data may suggest that exogenous GH affects the bone cellular mechanisms of Atlantic salmon postsmolts in such a way that their vertebrae increase in diameter but not length, not disturbing growth in body length. The GH and diet effects on lipid metabolism associated genes indicate a complex regulation of the lipids stored inside the vertebral column by endocrine and nutritional factors.
|
|
| 14. |
- Gennaro, Gisella, et al.
(författare)
-
Quality Controls in Digital Mammography protocol of the EFOMP Mammo Working group
- 2018
-
Ingår i: Physica Medica. - : Elsevier BV. - 1120-1797. ; 48, s. 55-64
-
Tidskriftsartikel (refereegranskat)abstract
- This article aims to present the protocol on Quality Controls in Digital Mammography published online in 2015 by the European Federation of Organisations for Medical Physics (EFOMP) which was developed by a Task Force under the Mammo Working Group. The main objective of this protocol was to define a minimum set of easily implemented quality control tests on digital mammography systems that can be used to assure the performance of a system within a set and acceptable range. Detailed step-by-step instructions have been provided, limiting as much as possible any misinterpretations or variations by the person performing. It is intended that these tests be implemented as part of the daily routine of medical physicists and system users throughout Europe in a harmonised way so allowing results to be compared. In this paper the main characteristics of the protocol are illustrated, including examples, together with a brief summary of the contents of each chapter. Finally, instructions for the download of the full protocol and of the related software tools are provided.
|
|
| 15. |
- Johansson, Jarkko, et al.
(författare)
-
Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan
- 2023
-
Ingår i: Cell Reports. - 2211-1247. ; 42:9
-
Tidskriftsartikel (refereegranskat)abstract
- Age-related alterations in D1-like dopamine receptor (D1DR) have distinct implications for human cognition and behavior during development and aging, but the timing of these periods remains undefined. Enabled by a large sample of in vivo assessments (n = 180, age 20 to 80 years of age, 50% female), we discover that age-related D1DR differences pivot at approximately 40 years of age in several brain regions. Focusing on the most age-sensitive dopamine-rich region, we observe opposing pre- and post-forties interrelations among caudate D1DR, cortico-striatal functional connectivity, and memory. Finally, particularly caudate D1DR differences in midlife and beyond, but not in early adulthood, associate with manifestation of white matter lesions. The present results support a model by which excessive dopamine modulation in early adulthood and insufficient modulation in aging are deleterious to brain function and cognition, thus challenging a prevailing view of monotonic D1DR function across the adult lifespan.
|
|
| 16. |
|
|
| 17. |
- KC, Ashish, 1982-, et al.
(författare)
-
Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.
- 2023
-
Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 7:4, s. 529-544
-
Tidskriftsartikel (refereegranskat)abstract
- Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
|
|
| 18. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 19. |
|
|
| 20. |
- Lunde, Kristin Aaser, et al.
(författare)
-
Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease
- 2018
-
Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 14:10, s. 1293-1301
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionBoth polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease.MethodsFour hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.ResultsA total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers.DiscussionGBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles.
|
|
| 21. |
- Lyng, Kristin, et al.
(författare)
-
Fetal brain injury in experimental intrauterine asphyxia and inflammation in Gottingen minipigs
- 2006
-
Ingår i: J Perinat Med. ; 34:3, s. 226-34
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine fetal brain injury in the Gottingen minipig following intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational length. METHODS: We performed laparotomy after anesthesia in six pregnant sows. We randomized 29 fetuses to one of four groups: pretreatment with saline or endotoxin followed by 30 min of umbilical cord occlusion or no occlusion. After 48 h we performed a re-laparotomy and examined the fetal brains. RESULTS: After total asphyxia, brain stem injury was present in the group pretreated with saline (P < 0.01 vs. controls) and with endotoxin (P < 0.005 vs. controls). Microglia activation was more marked in the brain stem (P < 0.05) and posterior white matter (P < 0.05) in the asphyxia group than in controls. Two of five fetuses in the asphyxia group had white matter injury, while no white matter lesions were found in the asphyxia/inflammation or endotoxin only groups. CONCLUSIONS: In this Gottingen minipig model, a species closer to humans than animals commonly used in experimental studies of perinatal brain injuries, intrauterine asphyxia following pretreatment with saline caused brain stem and white matter injury. This model can be further developed to study the impact of other intrauterine exposures on brain injury.
|
|
| 22. |
- Marouli, Eirini, et al.
(författare)
-
Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
|
|
| 23. |
- Merino, Jordi, et al.
(författare)
-
Quality of dietary fat and genetic risk of type 2 diabetes : individual participant data meta-analysis
- 2019
-
Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 366
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes.DESIGN Individual participant data meta-analysis.DATA SOURCES Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators.REVIEW METHODS Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score.RESULTS Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I-2 = 7.1%, tau(2) = 0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I-2 = 18.0%, tau(2) = 0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I-2 = 58.8%, tau(2) = 0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I-2 = 25.9%, tau(2) = 0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed.CONCLUSIONS These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.
|
|
| 24. |
- Munkvold, Bodil Karoline Ravn, et al.
(författare)
-
Variations in the management of diffuse low-grade gliomas : A Scandinavian multicenter study
- 2021
-
Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 8:6, s. 706-717
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected "high-risk" patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems.Methods. Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored.Results. A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy.Conclusions. Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.
|
|
| 25. |
- Nordin, Kristin, et al.
(författare)
-
DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes : A new window into cognitive aging
- 2022
-
Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 100:6, s. 1296-1320
-
Tidskriftsartikel (refereegranskat)abstract
- Concomitant exploration of structural, functional, and neurochemical brain mechanisms underlying age-related cognitive decline is crucial in promoting healthy aging. Here, we present the DopamiNe, Age, connectoMe, and Cognition (DyNAMiC) project, a multimodal, prospective 5-year longitudinal study spanning the adult human lifespan. DyNAMiC examines age-related changes in the brain’s structural and functional connectome in relation to changes in dopamine D1 receptor availability (D1DR), and their associations to cognitive decline. Critically, due to the complete lack of longitudinal D1DR data, the true trajectory of one of the most age-sensitive dopamine systems remains unknown. The first DyNAMiC wave included 180 healthy participants (20–80 years). Brain imaging included magnetic resonance imaging assessing brain structure (white matter, gray matter, iron), perfusion, and function (during rest and task), and positron emission tomography (PET) with the [11C]SCH23390 radioligand. A subsample (n = 20, >65 years) was additionally scanned with [11C]raclopride PET measuring D2DR. Age-related variation was evident for multiple modalities, such as D1DR; D2DR, and performance across the domains of episodic memory, working memory, and perceptual speed. Initial analyses demonstrated an inverted u-shaped association between D1DR and resting-state functional connectivity across cortical network nodes, such that regions with intermediate D1DR levels showed the highest levels of nodal strength. Evident within each age group, this is the first observation of such an association across the adult lifespan, suggesting that emergent functional architecture depends on underlying D1DR systems. Taken together, DyNAMiC is the largest D1DR study worldwide, and will enable a comprehensive examination of brain mechanisms underlying age-related cognitive decline.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Pedersen, Robin, et al.
(författare)
-
Dopamine D1-receptor organization contributes to functional brain architecture
- 2024
-
Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 44:11
-
Tidskriftsartikel (refereegranskat)abstract
- Recent work has recognized a gradient-like organization in cortical function, spanning from primary sensory to transmodal cortices. It has been suggested that this axis is aligned with regional differences in neurotransmitter expression. Given the abundance of dopamine D1-receptors (D1DR), and its importance for modulation and neural gain, we tested the hypothesis that D1DR organization is aligned with functional architecture, and that inter-regional relationships in D1DR co-expression modulate functional cross talk. Using the world's largest dopamine D1DR-PET and MRI database (N = 180%, 50% female), we demonstrate that D1DR organization follows a unimodal–transmodal hierarchy, expressing a high spatial correspondence to the principal gradient of functional connectivity. We also demonstrate that individual differences in D1DR density between unimodal and transmodal regions are associated with functional differentiation of the apices in the cortical hierarchy. Finally, we show that spatial co-expression of D1DR primarily modulates couplings within, but not between, functional networks. Together, our results show that D1DR co-expression provides a biomolecular layer to the functional organization of the brain.
|
|
| 29. |
- Pfeffer, M. A., et al.
(författare)
-
SO 2 emission rates and incorporation into the air pollution dispersion forecast during the 2021 eruption of Fagradalsfjall, Iceland
- 2024
-
Ingår i: Journal of Volcanology and Geothermal Research. - 0377-0273. ; 449
-
Tidskriftsartikel (refereegranskat)abstract
- During the low-effusion rate Fagradalsfjall eruption (19 March – 18 September 2021), the emission of sulfur dioxide (SO2) was frequently measured using ground-based UV spectrometers. The total SO2 emitted during the entire eruption was 970 ± 540 kt, which is only about 6% of the SO2 emitted during the similar length Holuhraun eruption (2014–2015). The eruption was divided into five phases based on visual observations, including the number of active vents and the occurrence of lava fountaining. The SO2 emission rate ranged from 44 ± 19 kg/s in Phase 2 to 85 ± 29 kg/s in Phase 5, with an average of 64 ± 34 kg/s for the entire eruption. There was notable variability in SO2 on short timescales, with measurements on 11 August 2021 ranging from 17 to 78 kg/s. SO2 flux measurements were made using scanning DOAS instruments located at different distances from and orientations relative to the eruption site augmented by traverses. Four hundred and forty-four scan and traverse measurements met quality criteria and were used, along with plume height and meteorological data, to calculate SO2 fluxes while accounting for wind-related uncertainties. A tendency for stronger SO2 flux concurrent with higher amplitude seismic tremor and the occurrence of lava fountaining was observed during Phases 4 and 5 which were characterized by intermittent crater activity including observable effusion of lava and gas release interspersed with long repose times. This tendency was used to refine the calculation of the amount of SO2 emitted during variably vigorous activity. The continuous seismic tremor time series was used to quantify how long during these eruption phases strong/weak activity was exhibited to improve the calculated SO2 flux during these Phases. The total SO2 emissions derived from field measurements align closely with results obtained by combining melt inclusion and groundmass glass analyses with lava effusion rate measurements (910 ± 230 kt SO2). Specifically, utilizing the maximum S content found in evolved melt inclusions and the least remaining S content in accompanying quenched groundmasses provides an identical result between field measurements and the petrological calculations. This suggests that the maximum SO2 release calculated from petrological estimates should be preferentially used to initialize gas dispersion models for basaltic eruptions when other measurements are lacking. During the eruption, the CALPUFF dispersion model was used to forecast ground-level exposure to SO2. The SO2 emission rates measured by DOAS were used as input for the dispersion model, with updates made when a significant change was measured. A detailed analysis of one mid-distance station over the entire eruption shows that the model performed very well at predicting the presence of volcanic SO2 when it was measured. However, it frequently predicted the presence of SO2 that was not measured and the concentrations forecasted had no correlation with the concentrations measured. Various approaches to improve the model forecast were tested, including updating plume height and SO2 flux source terms based on measurements. These approaches did not unambiguously improve the model performance but suggest that improvements might be achieved in more-polluted conditions.
|
|
| 30. |
- Rashad, Ahmad, et al.
(författare)
-
Inflammatory responses and tissue reactions to wood-Based nanocellulose scaffolds
- 2019
-
Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 97, s. 208-221
-
Tidskriftsartikel (refereegranskat)abstract
- Two wood-derived cellulose nanofibril (CNF) porous scaffolds were prepared by TEMPO-oxidation and carboxymethylation. The effects of these scaffolds on the production of inflammatory cytokines by human macrophage-like cells (U937) was profiled in vitro after 1 and 3 days and in subcutaneous tissues of rats after 4 and 30 days, using PCR and Multiplex arrays. Tissue culture plates (TCP) and gelatin scaffolds served as controls in vitro and in vivo respectively. After 3 days in vitro, there was no significant difference between the effects of CNF scaffolds and TCP on the production of chemokines/growth factors and pro-inflammatory cytokines. At day 4 in vivo there was significantly higher gene expression of the anti-inflammatory IL-1Ra in the CNF scaffolds than the gelatin scaffold. Production of IL-1β, IL-6, MCP-1, MIP-1α CXCL-1 and M-CSF was significantly less than in the gelatin, demonstrating an early mild inflammatory response. At day 30, both CNF scaffolds significantly stimulated the production of the anti-inflammatory cytokine IL-10. Unlike gelatin, neither CNF scaffold had degraded 180 days post-implantation. The slow degradation of CNF scaffolds resulted in a foreign body reaction, with high production of IL-1β, IL-2, TNF-α, IFN-ϒ, MCP-1, MIP-1α, M-CSF, VEGF cytokines and expression of MMP-9 gene. The surface chemistry of the CNF scaffolds elicited a modest effect on cytokine production and did not shift the inflammatory profile in vitro or in vivo. The decisive role in development of the foreign body reaction was the slow degradation of the CNF scaffolds.
|
|
| 31. |
- Saxena, Richa, et al.
(författare)
-
Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
-
Tidskriftsartikel (refereegranskat)abstract
- Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
|
|
| 32. |
|
|
| 33. |
- Semb, Gunvor, et al.
(författare)
-
A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
- 2017
-
Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
|
|
| 34. |
- Smith, Caren E., et al.
(författare)
-
Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent
- 2018
-
Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125. ; 62:3
-
Tidskriftsartikel (refereegranskat)abstract
- Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. Methods and results: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10−7), and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3’ of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10−8) such that each serving of low-fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.
|
|
| 35. |
- Stacey, Simon N, et al.
(författare)
-
A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
-
Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
|
|
| 36. |
- Stray-Pedersen, Asbjorg, et al.
(författare)
-
Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
-
Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
|
|
| 37. |
- Surakka, Ida, et al.
(författare)
-
A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol
- 2011
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:10, s. e1002333-
-
Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain similar to 25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79 x 10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
|
|
| 38. |
- Sørensen, Jeppe K., et al.
(författare)
-
Work stress and loss of years lived without chronic disease : an 18-year follow-up of 1.5 million employees in Denmark
- 2022
-
Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:4, s. 389-400
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to examine the association between exposure to work stress and chronic disease incidence and loss of chronic disease-free life years in the Danish workforce. The study population included 1,592,491 employees, aged 30–59 in 2000 and without prevalent chronic diseases. We assessed work stress as the combination of job strain and effort-reward imbalance using job exposure matrices. We used Cox regressions to estimate risk of incident hospital-diagnoses or death of chronic diseases (i.e., type 2 diabetes, coronary heart disease, stroke, cancer, asthma, chronic obstructive pulmonary disease, heart failure, and dementia) during 18 years of follow-up and calculated corresponding chronic disease-free life expectancy from age 30 to age 75. Individuals working in occupations with high prevalence of work stress had a higher risk of incident chronic disease compared to those in occupations with low prevalence of work stress (women: HR 1.04 (95% CI 1.02–1.05), men: HR 1.12 (95% CI 1.11–1.14)). The corresponding loss in chronic disease-free life expectancy was 0.25 (95% CI − 0.10 to 0.60) and 0.84 (95% CI 0.56–1.11) years in women and men, respectively. Additional adjustment for health behaviours attenuated these associations among men. We conclude that men working in high-stress occupations have a small loss of years lived without chronic disease compared to men working in low-stress occupations. This finding appeared to be partially attributable to harmful health behaviours. In women, high work stress indicated a very small and statistically non-significant loss of years lived without chronic disease.
|
|
| 39. |
- Vasiļjevs, Andrejs, et al.
(författare)
-
Creation of an Open Shared Language Resource Repository in the Nordic and Baltic Countries
- 2012
-
Ingår i: Proceedings of LREC 2012. - 9782951740877
-
Konferensbidrag (refereegranskat)abstract
- The META-NORD project has contributed to an open infrastructure for language resources (data and tools) under the META-NET umbrella. This paper presents the key objectives of META-NORD and reports on the results achieved in the first year of the project. META-NORD has mapped and described the national language technology landscape in the Nordic and Baltic countries in terms of language use, language technology and resources, main actors in the academy, industry, government and society; identified and collected the first batch of language resources in the Nordic and Baltic countries; documented, processed, linked, and upgraded the identified language resources to agreed standards and guidelines. The three horizontal multilingual actions in META-NORD are overviewed in this paper: linking and validating Nordic and Baltic wordnets, the harmonisation of multilingual Nordic and Baltic treebanks, and consolidating multilingual terminology resources across European countries. This paper also touches upon intellectual property rights for the sharing of language resources.
|
|
| 40. |
- Vikse, Rose, et al.
(författare)
-
Geographical distribution and prevalence of tick-borne encephalitis virus in questing Ixodes ricinus ticks and phylogeographic structure of the Ixodes ricinus vector in Norway
- 2020
-
Ingår i: Zoonoses and Public Health. - : WILEY. - 1863-1959 .- 1863-2378. ; 67:4, s. 370-381
-
Tidskriftsartikel (refereegranskat)abstract
- The tick-borne encephalitis virus (TBEV), a zoonotic flaviviral infection, is endemic in large parts of Norway and Eurasia. Humans are mainly infected with TBEV via bites from infected ticks. In Norway, the main geographical distribution of ticks is along the Norwegian coastline from southeast (similar to 59 degrees N) and up to the southern parts of Nordland County (similar to 65 degrees N). In this study, we collected ticks by flagging along the coast from ostfold County to Nordland County. By whole-genome sequencing of the mitochondrial genome of Ixodes ricinus, the phylogenetic tree suggests that there is limited phylogeographic structure both in Norway and in Europe. The overall TBEV prevalence is 0.3% for nymphs and 4.3% for adults. The highest estimated TBEV prevalence in adult ticks was detected in Rogaland and Vestfold County, while for nymphs it is highest in Vestfold, Vest-Agder and Rogaland. The present work is one of the largest studies on distribution and prevalence of TBEV in ticks in Scandinavia, showing that the virus is wider distributed in Norway than previously anticipated.
|
|
| 41. |
- Willer, Cristen J., et al.
(författare)
-
Discovery and refinement of loci associated with lipid levels
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
-
Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
|
|
| 42. |
- Zeggini, Eleftheria, et al.
(författare)
-
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
|
|
