| 1. |
- Bengtsson, Kenneth, et al.
(författare)
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Så kan Sverige bli ledande nation i resurseffektivitet
- 2016
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Ingår i: Dagens Nyheter. - 1101-2447. ; :2016-04-30
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Ny rapport. Det svenska näringslivet kan bli mer hållbart, resurssmart och därmed internationellt konkurrenskraftigt. Men för det behövs en tydlig politisk avsiktsförklaring och riktlinjer. Vi har listat sex områden där policyutveckling brådskar, skriver företrädare för näringsliv, forskning och myndigheter i en gemensam uppmaning.
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| 2. |
- Ek, Weronica E., et al.
(författare)
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Tea and coffee consumption in relation to DNA methylation in four European cohorts
- 2017
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 26:16, s. 3221-3231
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Tidskriftsartikel (refereegranskat)abstract
- Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed.After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated in men or in the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.
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| 3. |
- Gustafsson, Stefan, et al.
(författare)
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Markers of imminent myocardial infarction
- 2024
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Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590.
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case–cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.
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| 4. |
- Lind, Lars, et al.
(författare)
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Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample
- 2017
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 98, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p, p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.Results: Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allelewas 192 ng/g lipid (p= 1.5x10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19: 41520351; p= 2.2 x 10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p= 6.2 x 10(-9)) located 7 kb downstreamthe CYP2B6 gene (cg27089200, position chr19: 41531976). This CpG-sitewas also related to the lead SNP (p = 3.8 x 10(-35)), but mediated only 4% of the effect of the lead SNP on p, p'-DDE levels.Conclusion: Circulating levels of p, p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p, p'-DDE levels.
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| 5. |
- Lind, Lars, et al.
(författare)
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Longitudinal effects of aging on plasma proteins levels in older adults : associations with kidney function and hemoglobin levels
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels.MATERIAL AND METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured.RESULTS: Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships.CONCLUSION: The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.
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| 6. |
- Lind, Lars, et al.
(författare)
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Methylation-based estimated biological age and cardiovascular disease
- 2018
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Ingår i: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 48:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: DNA methylation changes over life at specific sites in the genome, which can be used to estimate "biological age." The aim of this population-based longitudinal cohort study was to investigate the association between estimated biological age and incident cardiovascular disease (CVD).MATERIALS AND METHODS: Based on formulas published by Hannum et al and Horvath et al, "biological age" was calculated using data from the Illumina 450k Bead Methylation chip in 832 participants free from cardiovascular disease in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between estimated biological and chronological age was calculated (DiffAge).RESULTS: During 10 years of follow-up, 153 incident cases of cardiovascular disease occurred. In the sex-adjusted analyses, the Horvath estimation of DiffAge was significantly related to incident cardiovascular disease (HR 1.040, 95% CI 1.010-1.071, P = .0079). Thus, for each year of increased biological age, a 4% increased risk of future cardiovascular disease was observed. This relationship was still significant following adjustment for the traditional risk factors sex, BMI, diabetes, HDL and LDL-cholesterol, systolic blood pressure and smoking (HR 1.033, 95% CI 1.004-1.063, P = .024). No such significant association was found using the Hannum formula.CONCLUSIONS: DNA methylation-based estimation of "biological age" per Horvath was associated with incident cardiovascular disease.
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| 7. |
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| 8. |
- Wang, Yunzhang, et al.
(författare)
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Epigenetic influences on aging : a longitudinal genome-wide methylation study in old Swedish twins
- 2018
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 13:9, s. 975-987
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Tidskriftsartikel (refereegranskat)abstract
- Age-related changes in DNA methylation were observed in cross-sectional studies, but longitudinal evidence is still limited. Here, we aimed to characterize longitudinal age-related methylation patterns using 1011 blood samples collected from 385 Swedish twins (age at entry: mean 69 and standard deviation 9.7, 73 monozygotic and 96 dizygotic pairs) up to five times (mean 2.6) over 20 years (mean 8.7). We identified 1316 age-associated methylation sites (P<1.3x10(-7)) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, 390 samples) (P<3.9x10(-5)), 594 in Lothian Birth Cohort (LBC, 3018 samples) (P<5.1x10(-5)) and 63 in both. Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other transcription factor binding sites. We further investigated genetic influences on methylation and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased with 6.4% over 10 years, where monozygotic twins had smaller intra-pair differences than dizygotic twins. In conclusion, we show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. The changes are under genetic influence, although this effect is independent of age. Moreover, methylation variability increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.
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| 9. |
- Aarnio, Mikko, et al.
(författare)
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Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The understanding of etiological mechanisms of whiplash associated disorder is still inadequate. Objective visualization and quantification of peripheral musculoskeletal injury and possible painful inflammation in whiplash associated disorder would facilitate diagnosis, strengthen patients’ subjective pain reports and aid clinical decisions eventually leading to better treatments. In the current study, we further evaluated the potential to use [11C]D-deprenyl PET/CT to visualize inflammation after whiplash injury. Sixteen patients with whiplash injury grade II were recruited at the emergency department and underwent [11C]D-deprenyl PET/CT in the acute phase and at 6 months after injury. Subjective pain levels, self rated neck disability and active cervical range of motion were recorded at each imaging session. Results showed that the molecular aspects of inflammation and possible tissue injuries after acute whiplash injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. An altered [11C]D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self rated disability during both imaging occasions. These findings may contribute to a better understanding of affected peripheral structures in whiplash injury and strengthens the idea that PET/CT detectable organic lesions in peripheral tissue may be relevant for the development of persistent pain and disability in whiplash injury.Perspective: This article presents a novel way of objectively visualizing possible structural damage and inflammation that cause pain and disability in whiplash injury. This PET method can bring an advance in pain research and eventually would facilitate the clinical management of patients in pain.
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| 10. |
- Aarnio, Mikko, et al.
(författare)
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Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl positron emission tomography and computed tomography
- 2022
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Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 163:3, s. 489-495
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [11C]-D-deprenyl positron emission tomography and computed tomography after acute whiplash injury and at 6-month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.
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