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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 4. |
- Bindler, Richard, et al.
(författare)
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Early medieval origins of iron mining and settlement in central Sweden : multiproxy analysis of sediment and peat records from the Norberg mining district
- 2011
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 38:2, s. 291-300
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Tidskriftsartikel (refereegranskat)abstract
- The historical Norberg mining district in central Sweden with its shallow, easily accessible iron ores figures prominently in the earliest documents from the 14th century concerning mining or metallurgy. This 1000-km2 district is considered to be one of the first areas in Sweden exploited for iron ores and, in fact, Europe’s oldest known blast furnace, Lapphyttan, is located in the Norberg district about 10 km from the mines in the village of Norberg (Norbergsby). Earlier archaeological excavations suggest the furnace was in operation as early as the 11th or 12th century (870 and 930 14C yr BP), and a number of other sites in the district have been dated to the 13th–15th centuries. Here, we have analyzed two lake sediment records (Kalven and Noren) from the village of Norberg and a peat record from Lapphyttan. The Lapphyttan peat record was radiocarbon dated, whereas the sediment from Kalven is annually laminated, which provides a fairly precise chronology. Our pollen data indicate that land use in the area began gradually as forest grazing by at least c. AD 1050, with indications of more widespread forest disturbance and cultivation from c. 1180 at Lapphyttan and 1250 at Kalven. Based on 206Pb/207Pb isotope ratios in Kalven’s varved sediment record, there is an indication of mining or metallurgy in the area c. 960, but likely not in immediate connection to our sites. Evidence of mining and metallurgy increases gradually from c. 1180 when there is a decline in 206Pb/207Pb ratios and an increase in charcoal particles at Lapphyttan, followed by increasing inputs of lithogenic elements in Noren’s sediment record indicating soil disturbance, which we attribute to the onset of mining the iron ore bodies surrounding Noren. From AD 1295 onwards evidence of mining and metallurgy are ubiquitous, and activities accelerate especially during the late 15th century; the maximum influence of Bergslagen ore lead (i.e., the minimum in 206Pb/207Pb isotope ratios) in both Kalven and Noren occurs c. 1490–1500, when also varve properties change in Kalven and in Noren sharp increases occur in the concentrations of a range of other ore-related metals (e.g., arsenic, cadmium, copper, iron, lead, mercury and zinc). From the 15th century onwards mining and metallurgy are the dominant feature of the sediment records.
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| 5. |
- Dugas, Lara R., et al.
(författare)
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Obesity-related metabolite profiles of black women spanning the epidemiologic transition
- 2016
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Ingår i: Metabolomics. - New York : Springer-Verlag New York. - 1573-3882 .- 1573-3890. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- In developed countries, specific metabolites have been associated with obesity and metabolic diseases, e.g. type 2 diabetes. It is unknown whether a similar profile persists across populations of African-origin, at increased risk for obesity and related diseases. In a cross-sectional study of normal-weight and obese black women (33.3 +/- 6.3 years) from the US (N = 69, 65 % obese), South Africa (SA, N = 97, 49 % obese) and Ghana (N = 82, 33 % obese) serum metabolite profiles were characterized via gas chromatography-time of flight/mass spectrometry. In US and SA women, BMI correlated with branched-chain and aromatic amino acids, as well as dopamine and aminoadipic acid. The relationship between BMI and lipid metabolites differed by site; BMI correlated positively with palmitoleic acid (16: 1) in the US; negatively with stearic acid (18: 0) in SA, and positively with arachidonic acid (20: 4) in Ghana. BMI was also positively associated with sugar-related metabolites in the US; i.e. uric acid, and mannitol, and with glucosamine, glucoronic acid and mannitol in SA. While we identified a common amino acid metabolite profile associated with obesity in black women from the US and SA, we also found site-specific obesity-related metabolites suggesting that the local environment is a key moderator of obesity.
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| 6. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 7. |
- Hadrévi, Jenny, 1977-, et al.
(författare)
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Work-Related Stress Was Not Associated with Increased Cancer Risk in a Population-Based Cohort Setting
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stress is a commonly perceived cause of cancer, but the evidence to date is limited and inconclusive. We examined work-related stress in relation to cancer incidence in a population-based cohort, with outcome data from Swedish national registries.Methods: The study population included 113,057 participants in the Västerbotten Intervention Programme. HRs were estimated using Cox proportional hazards regression, for cancer overall and for types with ≥500 cases, and adjusting for several potential confounders. The primary exposure was prediagnostic work-related stress, using the well established Karasek job demand/control model. Demand and control variables were dichotomized at the median, and participants were classified according to combinations of these categories. We also considered social network and aspects of quality of life.Results: "High-strain" work (high demand/low control) was not associated with cancer risk compared with "low-strain" work (low demand/high control): multivariable HR 1.01 [95% confidence interval (CI), 0.94-1.08] for men and 0.99 (95% CI, 0.92-1.07) for women. Results were also null for most cancer types assessed: prostate, breast, colorectal, lung, and gastrointestinal (GI). The risk of GI cancer was lower for "passive" (low demand/low control) versus "low-strain" work, particularly for colorectal cancer in women: multivariable HR 0.71 (95% CI, 0.55-0.91), but statistical significance was lost after adjustment for multiple testing.Conclusions: The findings of this population-based, cohort study do not support a role for work-related stress in determining cancer risk.Impact: This study helps fill an important knowledge gap given the common concern about stress as a risk factor for cancer.
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| 8. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 9. |
- Linder, Jan, 1957-, et al.
(författare)
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Degenerative changes were common in brain magnetic resonance imaging in patients with newly diagnosed Parkinson's disease in a population-based cohort
- 2009
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Ingår i: Journal of Neurology. - Berlin : Springer. - 0340-5354 .- 1432-1459. ; 256:10, s. 1671-1680
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate newly diagnosed patients with Parkinson's disease (PD) with structural magnetic resonance imaging (MRI), to compare them with healthy controls, to relate the findings to clinical subtypes - tremor dominant (TD) or postural instability and gait difficulty (PIGD) - and to investigate the relationship between both the duration from onset of symptoms to diagnosis and the severity of symptoms and the MRI findings. Patients with a definite PD diagnosis were compared to patients with a probable PD diagnosis. We hypothesized that the PIGD subtype, the probable PD group, a greater symptom severity and a longer symptom duration would all be associated with more frequent pathological findings. Sixty-six PD patients were included and examined with MRI, 35 with the PIGD subtype and 23 with the TD subtype. Fifty-three had definite PD and 13 probable PD. Thirty healthy individuals, matched for age and sex, served as controls. Degenerative changes in the cerebellar cortex and the superior cerebellar peduncle were significantly more common in the probable PD group than in the controls, suggesting the possibility of an emerging atypical parkinsonian disorder. No significant MRI differences were found between definite PD and controls, between definite PD and probable PD, nor between PIGD and TD. No significant associations were found between duration to diagnosis and MRI results, nor between severity of symptoms and MRI results. Thus, although pathological MRI findings were common they can not be used to separate subgroups of PD in newly diagnosed patients.
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| 10. |
- Macphail, Richard I., et al.
(författare)
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Microstratigraphy (soil micromorphology and microchemistry, soil chemistry, and magnetic susceptibility)
- 2017
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Ingår i: Avaldsnes - a sea-kings' manor in first-millennium western scandinavia. - : Walter de Gruyter. - 9783110421088 - 9783110425789 ; , s. 379-420
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Bokkapitel (refereegranskat)abstract
- The Avaldsnes site was intensively studied employing soil chemistry, magnetic susceptibility (352 samples), and soil micromorphology (74 thin sections), complemented by SEM/EDS investigations on thin sections; a pollen profile and a single organic chemistry sample were also studied. Six archaeological areas were investigated employing samples from both profile and grid-sampled areas.
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