| 1. |
- Allentoft, Morten E., et al.
(författare)
-
100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
|
|
| 2. |
- Allentoft, Morten E., et al.
(författare)
-
Population genomics of post-glacial western Eurasia
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
-
Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
|
|
| 3. |
- Framke, Elisabeth, et al.
(författare)
-
Contribution of income and job strain to the association between education and cardiovascular disease in 1.6 million Danish employees
- 2020
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 41:11, s. 1164-1178
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: We examined the extent to which associations between education and cardiovascular disease (CVD) morbidity and mortality are attributable to income and work stress.Methods and results: We included all employed Danish residents aged 30–59 years in 2000. Cardiovascular disease morbidity analyses included 1 638 270 individuals, free of cardiometabolic disease (CVD or diabetes). Mortality analyses included 41 944 individuals with cardiometabolic disease. We assessed education and income annually from population registers and work stress, defined as job strain, with a job-exposure matrix. Outcomes were ascertained until 2014 from health registers and risk was estimated using Cox regression. During 10 957 399 (men) and 10 776 516 person-years (women), we identified 51 585 and 24 075 incident CVD cases, respectively. For men with low education, risk of CVD was 1.62 [95% confidence interval (CI) 1.58–1.66] before and 1.46 (95% CI 1.42–1.50) after adjustment for income and job strain (25% reduction). In women, estimates were 1.66 (95% CI 1.61–1.72) and 1.53 (95% CI 1.47–1.58) (21% reduction). Of individuals with cardiometabolic disease, 1736 men (362 234 person-years) and 341 women (179 402 person-years) died from CVD. Education predicted CVD mortality in both sexes. Estimates were reduced with 54% (men) and 33% (women) after adjustment for income and job strain.Conclusion: Low education predicted incident CVD in initially healthy individuals and CVD mortality in individuals with prevalent cardiometabolic disease. In men with cardiometabolic disease, income and job strain explained half of the higher CVD mortality in the low education group. In healthy men and in women regardless of cardiometabolic disease, these factors explained 21–33% of the higher CVD morbidity and mortality.
|
|
| 4. |
- Hellem, Marie N.N., et al.
(författare)
-
Decreased CSF oxytocin relates to measures of social cognitive impairment in Huntington's disease patients
- 2022
-
Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 99, s. 23-29
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Huntington's disease (HD) is an inherited neurodegenerative disease with motor, cognitive and psychiatric symptoms. Non-motor symptoms like depression and altered social cognition are proposed to be caused by dysfunction of the hypothalamus. We measured the hypothalamic neuropeptide oxytocin in plasma and cerebrospinal fluid (CSF) in a cohort of HD gene expansion carriers (HDGECs), compared the levels to healthy HD family controls and correlated oxytocin levels to disease progression and social cognition. Methods: We recruited 113 HDGECs and 33 controls. Psychiatric and cognitive symptoms were evaluated, and social cognition was assessed with the Emotion Hexagon test, Reading the Mind in the Eyes and The Awareness of Social Inference Test. The levels of oxytocin in CSF and blood were analyzed by radioimmunoassay. Results: We found the level of oxytocin in CSF to be significantly lower by 33.5% in HDGECs compared to controls (p = 0.016). When dividing the HDGECs into groups with or without cognitive impairment, we found the oxytocin level to be significantly lower by 30.3% in the HDGECs with cognitive symptoms (p = 0.046). We found a statistically significant correlation between the level of oxytocin and scores on social cognition (Reading the Mind in the Eyes p = 0.0019; Emotion Hexagon test: p = 0.0062; The Awareness of Social Inference Test: p = 0.002). Conclusions: This is the first study to measure oxytocin in the CSF of HDGECs. We find that HDGECs have a significantly lower level of oxytocin compared to controls, and that the level of oxytocin may represent an objective and comparable measure that could be used as a state biomarker for impairment of social cognition. We suggest treatment trials to evaluate a potential effect of oxytocin on social cognition in HD.
|
|
| 5. |
- Knutsson, Linda, et al.
(författare)
-
Absolute quantification of cerebral blood flow: correlation between dynamic susceptibility contrast MRI and model-free arterial spin labeling.
- 2010
-
Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X. ; 28:1, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare absolute cerebral blood flow (CBF) estimates obtained by model-free arterial spin labeling (ASL) and dynamic susceptibility contrast MRI (DSC-MRI), corrected for partial volume effects (PVEs). METHODS: CBF was measured using DSC-MRI and model-free ASL (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) at 3 T in 15 subjects with brain tumor, and the two modalities were compared with regard to CBF estimates in normal gray matter (GM) and DSC-to-ASL CBF ratios in selected tumor regions. The DSC-MRI CBF maps were calculated using a global arterial input function (AIF) from the sylvian-fissure region, but, in order to minimize PVEs, the AIF time integral was rescaled by a venous output function time integral obtained from the sagittal sinus. RESULTS: In GM, the average DSC-MRI CBF estimate was 150+/-45 ml/(min 100 g) (mean+/-SD) while the corresponding ASL CBF was 44+/-10 ml/(min 100 g). The linear correlation between GM CBF estimates obtained by DSC-MRI and ASL was r=.89, and observed DSC-to-ASL CBF ratios differed by less than 3% between GM and tumor regions. CONCLUSIONS: A satisfactory positive linear correlation between the CBF estimates obtained by model-free ASL and DSC-MRI was observed, and DSC-to-ASL CBF ratios showed no obvious tissue dependence.
|
|
| 6. |
- Rugulies, Reiner, et al.
(författare)
-
Persistent and changing job strain and risk of coronary heart disease : A population-based cohort study of 1.6 million employees in Denmark
- 2020
-
Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 46:5, s. 498-507
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives This study aimed to examine the association between job strain and incident coronary heart disease (CHD) in Denmark, while accounting for changes of job strain.Methods We included all employees residing in Denmark in 2000, aged 30–59 years with no prevalent CHD (N=1 660 150). We determined exposure to job strain from 1996–2009 using a job exposure matrix (JEM) with annual updates. Follow-up for incident CHD was from 2001–2010 via linkage to health records. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between job strain and incident CHD.Results During 16.1 million person-years, we identified 24 159 incident CHD cases (15.0 per 10 000 person-years). After adjustment for covariates, job strain in 2000 predicted onset of CHD during a mean follow-up of 9.71 years (HR 1.10, 95% CI 1.07–1.13). When analyzing changes in job strain from one year to the next and CHD in the subsequent year, persistent job strain (HR 1.07, 95% CI 1.03–1.10), onset of job strain (HR 1.20, 95% CI 1.12–1.29) and removal of strain (HR 1.20, 95% CI 1.12–1.28) were associated with higher CHD incidence compared to persistent no job strain. Associations were similar among men and women.Conclusions Job strain is associated with a higher risk of incident CHD in Denmark. As we used a JEM, we can rule out reporting bias. However, under- or overestimation of associations is possible due to non-differential misclassification of job strain and residual confounding by socioeconomic position.
|
|
| 7. |
- van Westen, Danielle, et al.
(författare)
-
Correlation between arterial blood volume obtained by arterial spin labelling and cerebral blood volume in intracranial tumours.
- 2011
-
Ingår i: Magma. - : Springer Science and Business Media LLC. - 1352-8661. ; 24, s. 211-223
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare measurements of the arterial blood volume (aBV), a perfusion parameter calculated from arterial spin labelling (ASL), and cerebral blood volume (CBV), calculated from dynamic susceptibility contrast (DSC) MRI. In the clinic, CBV is used for grading of intracranial tumours. MATERIALS AND METHODS: Estimates of aBV from the model-free ASL technique quantitative STAR labelling of arterial regions (QUASAR) experiment and of DSC-CBV were obtained at 3T in ten patients with eleven tumours (three grade III gliomas, four glioblastomas and four meningiomas, two in one patient). Parametric values of aBV and CBV were determined in the tumour as well as in normal grey matter (GM), and tumour-to-GM aBV and CBV ratios were calculated. RESULTS: In a 4-pixel ROI representing maximal tumour values, the coefficient of determination R (2) was 0.61 for the comparison of ASL-based aBV tumour-to-GM ratios and DSC-MRI-based CBV tumour-to-GM ratios and 0.29 for the comparison of parametric values of ASL-aBV and DSC-CBV, under the assumption of proportionality. Both aBV and CBV showed a non-significant tendency to increase when going from grade III gliomas to glioblastomas to meningiomas. CONCLUSION: These results suggest that measurement of aBV is a potential tool for non-invasive assessment of blood volume in intracranial tumours.
|
|
