| 1. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 2. |
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| 4. |
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| 5. |
- Pulit, S. L., et al.
(author)
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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
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In: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
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Journal article (peer-reviewed)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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| 10. |
- Feigin, Valery L., et al.
(author)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Journal article (peer-reviewed)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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| 13. |
- Aghion, S., et al.
(author)
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A moiré deflectometer for antimatter
- 2014
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 5
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Journal article (peer-reviewed)abstract
- The precise measurement of forces is one way to obtain deep insight into the fundamental interactions present in nature. In the context of neutral antimatter, the gravitational interaction is of high interest, potentially revealing new forces that violate the weak equivalence principle. Here we report on a successful extension of a tool from atom optics—the moiré deflectometer—for a measurement of the acceleration of slow antiprotons. The setup consists of two identical transmission gratings and a spatially resolving emulsion detector for antiproton annihilations. Absolute referencing of the observed antimatter pattern with a photon pattern experiencing no deflection allows the direct inference of forces present. The concept is also straightforwardly applicable to antihydrogen measurements as pursued by the AEgIS collaboration. The combination of these very different techniques from high energy and atomic physics opens a very promising route to the direct detection of the gravitational acceleration of neutral antimatter.
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| 14. |
- Ariga, T., et al.
(author)
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Measuring GBAR with emulsion detector
- 2014
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In: International Journal of Modern Physics, Conference Series. - : World Scientific. - 2010-1945. ; 30
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Journal article (peer-reviewed)
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| 15. |
- Sampson, Joshua N., et al.
(author)
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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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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)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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| 16. |
- Deo, R., et al.
(author)
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Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants
- 2013
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In: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 10:3, s. 401-408
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Journal article (peer-reviewed)abstract
- BACKGROUND Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE To identify novel genetic variants associated with resting heart rate in African Americans. METHODS Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of singe nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P <= 2.5 x 10(-8)). RESULTS Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98 x 10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.
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| 17. |
- Macfarlane, M. D., et al.
(author)
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Shape abnormalities of the caudate nucleus correlate with poorer gait and balance: Results from a subset of the ladis study
- 2015
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In: The American journal of geriatric psychiatry. - : Elsevier BV. - 1064-7481. ; 23:1, s. 59-
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Journal article (peer-reviewed)abstract
- Objective Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in frontostriatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter hyperintensities (WMHs) on magnetic resonance imaging has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction. Methods Magnetic resonance imaging scans and clinical gait/balance data (scores from the Short Physical Performance Battery [SPPB]) were sourced from 66 subjects in the previously published LADIS trial, performed in nondisabled individuals older than age 65 years with WMHs at study entry. Data were obtained at study entry and at 3-year follow-up. Caudate nuclei and putamina were manually traced using a previously published method and volumes calculated. The relationships between volume and physical performance on the SPPB were investigated with shape analysis using the spherical harmonic shape description toolkit. Results There was no correlation between the severity of WMHs and striatal volumes. Caudate nuclei volume correlated with performance on the SPPB at baseline but not at follow-up, with subsequent shape analysis showing left caudate changes occurred in areas corresponding to inputs of the dorsolateral prefrontal, premotor, and motor cortex. There was no correlation between putamen volumes and performance on the SPPB. Conclusion Disruption in frontostriatal circuits may play a role in mediating poorer physical performance in individuals with WMHs. Striatal volume and shape changes may be suitable biomarkers for functional changes in this population. © 2015 American Association for Geriatric Psychiatry.
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| 18. |
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| 19. |
- Berndt, Sonja, I, et al.
(author)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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In: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Journal article (peer-reviewed)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 20. |
- van Setten, Jessica, et al.
(author)
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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
- 2018
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
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| 21. |
- Bonaca, M. P., et al.
(author)
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Reduction in subtypes and sizes of myocardial infarction with ticagrelor in PEGASUS-TIMI 54
- 2018
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In: Journal of the American Heart Association. - 2047-9980. ; 7:22
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Journal article (peer-reviewed)abstract
- Background-—Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUSTIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results-—MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow-up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention–related (Type 4a) and coronary artery bypass graft–related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥1009 upper limit of normal. A total of 21% (224) were ST-segment–elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72–0.95, P=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥1009 upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53–0.92, P=0.0096) and a 40% reduction in ST-segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46–0.78, P=0.0002). Conclusions-—In stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST-segment elevation MI. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562. © 2018 The Authors.
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| 22. |
- Butler, Anne M., et al.
(author)
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Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts
- 2012
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In: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 639-646
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Journal article (peer-reviewed)abstract
- Background-The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results-We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and approximate to 2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (lambda range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (lambda: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0x10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0x10-8). Conclusions-This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent. (Circ Cardiovasc Genet. 2012;5:639-646.)
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| 23. |
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| 24. |
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| 25. |
- Smith, Gustav, et al.
(author)
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The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans.
- 2012
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In: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 647-655
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Journal article (peer-reviewed)abstract
- BACKGROUND: -Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. METHODS AND RESULTS: -First, individual estimates of African and European ancestry were inferred from genome-wide single nucleotide polymorphism (SNP) data in seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5x10(-8)) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2x10(-15)) and ATP1B1 (rs1320976, p=2x10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low p-values (p<10(-5)) were observed for SNPs at several other loci previously identified in GWA studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF and PLN. CONCLUSIONS: -We observed no difference in duration of cardiac repolarization with global genetic indices of African ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans.
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| 26. |
- Talibov, M, et al.
(author)
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Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring: findings from the Childhood Leukaemia International Consortium (CLIC)
- 2019
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In: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 76:10, s. 746-753
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Journal article (peer-reviewed)abstract
- Previously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent. We therefore evaluated this question within the Childhood Leukemia International Consortium.MethodsWe pooled 11 case–control studies including 9723 childhood leukaemia cases and 17 099 controls. Parental occupational ELF-MF exposure was estimated by linking jobs to an ELF-MF job-exposure matrix (JEM). Logistic regression models were used to estimate ORs and 95% CIs in pooled analyses and meta-analyses.ResultsORs from pooled analyses for paternal ELF-MF exposure >0.2 microtesla (µT) at conception were 1.04 (95% CI 0.95 to 1.13) for ALL and 1.06 (95% CI 0.87 to 1.29) for AML, compared with ≤0.2 µT. Corresponding ORs for maternal ELF-MF exposure during pregnancy were 1.00 (95% CI 0.89 to 1.12) for ALL and 0.85 (95% CI 0.61 to 1.16) for AML. No trends of increasing ORs with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses.ConclusionsIn this large international dataset applying a comprehensive quantitative JEM, we did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia.
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| 30. |
- Settimi, Laura, et al.
(author)
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Cancer risk among female agricultural workers : a multi-center case-control study
- 1999
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In: American Journal of Industrial Medicine. - 0271-3586 .- 1097-0274. ; 36:1, s. 135-141
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Journal article (peer-reviewed)abstract
- BackgroundCancer risk among women engaged in farming has been poorly investigated. This group of female workers is of particular interest, however, since they may experience exposure to several potential agricultural hazards.MethodsA hospital-based case-control study was conducted in five Italian rural areas to examine the association between cancer and farming among women. The areas selected were located in three different regions (i.e., Piedmont, Tuscany, and Emilia-Romagna). The following cancer sites were selected for the study: stomach, colon, rectum, lung, skin melanoma, skin non-melanoma, breast, cervix and corpus uteri, ovary, bladder, kidney. Cases of non-Hodgkin's lymphoma were also included. Altogether, 1,044 newly diagnosed cases aged 20–75 years were ascertained from hospital records from March 1990 to September 1992, and for 945 of them detailed information was collected by a standard questionnaire. The analyses of data were performed comparing each case series to a reference group drawn from among the other sites. Unconditional logistic regression models were used in the statistical analyses.ResultsStatistically significant increased risks in association with farming were estimated for skin melanoma (OR 2.7, 95% CI 1.2–5.8) and bladder cancer (OR 2.7, 95% CI 1.2–6.1). Lung cancer was also found increased but not at a statistically significant level (OR 1.7, 95% CI 0.7–4.4). An OR lower than unity was observed for postmenopausal breast cancer (OR 0.4, 95% CI 0.3–0.7).ConclusionsThe present study suggests that women in farming might experience increased risk of cancers, not usually found in excess among male farmers, as well as a protective effect for postmenopausal breast cancer. The role of different patterns of exposure or gender specific responses should be considered in further studies.
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| 31. |
- Smith, Gustav, et al.
(author)
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Genome-Wide Association Studies of the PR Interval in African Americans.
- 2011
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:2
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Journal article (peer-reviewed)abstract
- The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10(-8)) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta = 5.1 msec per minor allele, 95% CI = 4.1-6.1, p = 3×10(-23)). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8-3.0, p = 3×10(-16)) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans.
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| 32. |
- Wade, C. M., et al.
(author)
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Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
- 2009
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5954, s. 865-867
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Journal article (peer-reviewed)abstract
- We report a high-quality draft sequence of the genome of the horse ( Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
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| 35. |
- Guimaraes, K. S. D., et al.
(author)
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Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves lipid profile, insulin sensitivity and gut microbiota diversity in dyslipidemic dams and protects male offspring against cardiovascular dysfunction in later life
- 2020
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In: Food & Function. - : Royal Society of Chemistry (RSC). - 2042-6496 .- 2042-650X. ; 11:10, s. 8939-8950
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Journal article (peer-reviewed)abstract
- Background and aim: Maternal dyslipidemia is recognized as a risk factor for the development of arterial hypertension (AH) and cardiovascular dysfunction in offspring. Here we evaluated the effects of probiotic administration of a specific strain of Lactiplantibacillus plantarum(WJL) during pregnancy and lactation on gut microbiota and metabolic profile in dams fed with a high-fat and high-cholesterol (HFHC) diet and its long-term effects on the cardiovascular function in male rat offspring.Methods and results: Pregnant Wistar rats were allocated into three groups: dams fed a control diet (CTL = 5), dams fed a HFHC diet (DLP = 5) and dams fed a HFHC diet and receivingL. plantarum WJL during pregnancy and lactation (DLP-Lp(WJL)).L. plantarum WJL (1 x 10(9)CFU) or vehicle (NaCl, 0.9%) was administered daily by oral gavage for 6 weeks, covering the pregnancy and lactation periods. After weaning, male offspring received a standard diet up to 90 days of life. Biochemical measurements and gut microbiota were evaluated in dams. In male offspring, blood pressure (BP), heart rate (HR) and vascular reactivity were evaluated at 90 days of age. Dams fed with a HFHC diet during pregnancy and lactation had increased lipid profile and insulin resistance and showed dysbiotic gut microbiota. Administration of L. plantarum WJL to dams having maternal dyslipidemia improved gut microbiota composition, lipid profile and insulin resistance in them. Blood pressure was augmented and vascular reactivity was impaired with a higher contractile response and a lower response to endothelium-dependent vasorelaxation in DLP male offspring. In contrast, male offspring of DLP-Lp(WJL) dams had reduced blood pressure and recovered vascular function in later life.Conclusion: Administration ofL. plantarum WJL during pregnancy and lactation in dams improved gut microbiota diversity, reduced maternal dyslipidemia and prevented cardiovascular dysfunction in male rat offspring.
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| 36. |
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| 37. |
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| 38. |
- Magnani, G., et al.
(author)
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Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial
- 2016
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In: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 37:4, s. 400-408
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Journal article (peer-reviewed)abstract
- AIMS: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). METHODS AND RESULTS: Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m2 pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. >/=60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). CONCLUSION: In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor.
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| 39. |
- Maldonado, Pablo, et al.
(author)
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Crystal dynamics and thermal properties of neptunium dioxide
- 2016
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In: PHYSICAL REVIEW B. - 2469-9950. ; 93:14
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Journal article (peer-reviewed)abstract
- We report an experimental and theoretical investigation of the lattice dynamics and thermal properties of the actinide dioxide NpO2. The energy-wave-vector dispersion relation for normal modes of vibration propagating along the [001], [110], and [111] high-symmetry lines in NpO2 at room temperature has been determined by measuring the coherent one-phonon scattering of x rays from an similar to 1.2-mg single-crystal specimen, the largest available single crystal for this compound. The results are compared against ab initio phonon dispersions computed within the first-principles density functional theory in the generalized gradient approximation plus Hubbard U correlation (GGA+U) approach, taking into account third-order anharmonicity effects in the quasiharmonic approximation. Good agreement with the experiment is obtained for calculations with an on-site Coulomb parameter U = 4 eV and Hund's exchange J = 0.6 eV in line with previous electronic structure calculations. We further compute the thermal expansion, heat capacity, thermal conductivity, phonon linewidth, and thermal phonon softening, and compare with available experiments. The theoretical and measured heat capacities are in close agreement with another. About 27% of the calculated thermal conductivity is due to phonons with energy higher than 25 meV (similar to 6 THz), suggesting an important role of high-energy optical phonons in the heat transport. The simulated thermal expansion reproduces well the experimental data up to about 1000 K, indicating a failure of the quasiharmonic approximation above this limit.
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| 40. |
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| 41. |
- Muser, Daniele, et al.
(author)
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Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias
- 2021
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 143:14, s. 1359-1373
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Journal article (peer-reviewed)abstract
- Background: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. Methods: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. Results: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). Conclusions: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.
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| 42. |
- Muser, Daniele, et al.
(author)
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Risk Stratification of Patients With Apparently Idiopathic Premature Ventricular Contractions A Multicenter International CMR Registry
- 2020
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In: JACC. - : ELSEVIER. - 2405-500X .- 2405-5018. ; 6:6, s. 722-735
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Journal article (peer-reviewed)abstract
- OBJECTIVES This study investigated the prevalence and prognostic significance of concealed myocardial abnormalities identified by cardiac magnetic resonance (CMR) imaging in patients with apparently idiopathic premature ventricular contractions (PVCs). BACKGROUND The rote of CMR imaging in patients with frequent PVCs and otherwise negative diagnostic workup is uncertain. METHODS This was a multicenter, international study that included 518 patients (age 44 +/- 15 years; 57% men) with frequent (>1,000/24 h) PVCs and negative routine diagnostic workup. Patients underwent a comprehensive CMR protocol including late gadolinium enhancement imaging for detection of necrosis and/or fibrosis. The study endpoint was a composite of sudden cardiac death, resuscitated cardiac arrest, and nonfatal episodes of ventricular fibrillation or sustained ventricular tachycardia that required appropriate implantable cardioverter-defibrillator therapy. RESULTS Myocardial abnormalities were found in 85 (16%) patients. Mate gender (odds ratio [OR]: 4.28; 95% confidence interval [CI]: 2.06 to 8.93; p = 0.01), family history of sudden cardiac death and/or cardiomyopathy (OR: 3.61; 95% CI: 1.33 to 9.82; p = 0.01), multifocat PVCs (OR: 11.12; 95% CI: 4.35 to 28.46; p < 0.01), and non-left bundle branch block inferior axis morphology (OR: 14.11; 95% CI: 7.35 to 27.07; p < 0.01) were alt significantly related to the presence of myocardial abnormalities. After a median follow-up of 67 months, the composite endpoint occurred in 26 (5%) patients. Subjects with myocardial abnormalities on CMR had a higher incidence of the composite outcome (n = 25; 29%) compared with those without abnormalities (n = 1; 0.2%; p < 0.01). CONCLUSIONS CMR can identify concealed myocardial abnormalities in 16% of patients with apparently idiopathic frequent PVCs. Presence of myocardial abnormalities on CMR predict worse clinical outcomes. (C) 2019 by the American College of Cardiology Foundation.
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| 43. |
- Wang, Sophia S., et al.
(author)
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HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
- 2018
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:14, s. 4086-4096
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Journal article (peer-reviewed)abstract
- A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.
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| 44. |
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| 45. |
- Din, Lennox, et al.
(author)
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Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes
- 2019
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In: Genetic Epidemiology. - : WILEY. - 0741-0395 .- 1098-2272. ; 43:7, s. 844-863
-
Journal article (peer-reviewed)abstract
- Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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| 46. |
- Ellinor, Patrick T., et al.
(author)
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Meta-analysis identifies six new susceptibility loci for atrial fibrillation
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:6, s. 88-670
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Journal article (peer-reviewed)abstract
- Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
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| 47. |
- Lim, J. A., et al.
(author)
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Unexpected phase locking of magnetic fluctuations in the multi-k magnet USb
- 2013
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In: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 87:6
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Journal article (peer-reviewed)abstract
- The spin waves in the multi-k antiferromagnet USb soften and become quasielastic well below the antiferromagnetic ordering temperature T-N. This occurs without a magnetic or structural transition. It has been suggested that this change is in fact due to dephasing of the different multi-k components: a switch from 3-k to 1-k behavior. In this work, we use inelastic neutron scattering with tridirectional polarization analysis to probe the quasielastic magnetic excitations and reveal that the 3-k structure does not dephase. More surprisingly, the paramagnetic correlations also maintain the same clear phase correlations well above T-N ( up to at least 1.4T(N)). DOI: 10.1103/PhysRevB.87.064421
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| 48. |
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| 49. |
- Magnani, F, et al.
(author)
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The human footprint in the carbon cycle of temperate and boreal forests
- 2007
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In: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885. ; 447, s. 848-850
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Journal article (peer-reviewed)abstract
- Temperate and boreal forests in the Northern Hemisphere cover an area of about 2 times 107 square kilometres and act as a substantial carbon sink (0.6–0.7 petagrams of carbon per year)1. Although forest expansion following agricultural abandonment is certainly responsible for an important fraction of this carbon sink activity, the additional effects on the carbon balance of established forests of increased atmospheric carbon dioxide, increasing temperatures, changes in management practices and nitrogen deposition are difficult to disentangle, despite an extensive network of measurement stations2, 3. The relevance of this measurement effort has also been questioned4, because spot measurements fail to take into account the role of disturbances, either natural (fire, pests, windstorms) or anthropogenic (forest harvesting). Here we show that the temporal dynamics following stand-replacing disturbances do indeed account for a very large fraction of the overall variability in forest carbon sequestration. After the confounding effects of disturbance have been factored out, however, forest net carbon sequestration is found to be overwhelmingly driven by nitrogen deposition, largely the result of anthropogenic activities5. The effect is always positive over the range of nitrogen deposition covered by currently available data sets, casting doubts on the risk of widespread ecosystem nitrogen saturation6 under natural conditions. The results demonstrate that mankind is ultimately controlling the carbon balance of temperate and boreal forests, either directly (through forest management) or indirectly (through nitrogen deposition).
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| 50. |
- Magnani, N., et al.
(author)
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Magnetic Polarization of the Americium J=0 Ground State in AmFe2
- 2015
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 114:9
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Journal article (peer-reviewed)abstract
- Trivalent americium has a nonmagnetic (J = 0) ground state arising from the cancellation of the orbital and spin moments. However, magnetism can be induced by a large molecular field if Am3+ is embedded in a ferromagnetic matrix. Using the technique of x-ray magnetic circular dichroism, we show that this is the case in AmFe2. Since < J(z)> = 0, the spin component is exactly twice as large as the orbital one, the total Am moment is opposite to that of Fe, and the magnetic dipole operator < T-z > can be determined directly; we discuss the progression of the latter across the actinide series.
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