| 1. |
- Mishra, A., et al.
(author)
-
Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
-
Journal article (peer-reviewed)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
|
|
| 2. |
- Justice, A. E., et al.
(author)
-
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
|
|
| 3. |
- Davies, G., et al.
(author)
-
Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
-
Journal article (peer-reviewed)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
|
|
| 4. |
|
|
| 5. |
- Barausse, Enrico, et al.
(author)
-
Prospects for fundamental physics with LISA
- 2020
-
In: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
-
Journal article (other academic/artistic)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Lumbers, R. T., et al.
(author)
-
The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
-
In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
-
Journal article (peer-reviewed)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Davies, G., et al.
(author)
-
Genetic contributions to variation in general cognitive function : a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
- 2015
-
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 20:2, s. 183-192
-
Journal article (peer-reviewed)abstract
- General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
|
|
| 12. |
|
|
| 13. |
- Kaptoge, S., et al.
(author)
-
World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
-
In: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
-
Journal article (peer-reviewed)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
|
|
| 14. |
- Shah, S, et al.
(author)
-
Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
-
Journal article (peer-reviewed)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
|
|
| 15. |
|
|
| 16. |
- Chauhan, G., et al.
(author)
-
Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
- 2019
-
In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:5
-
Journal article (peer-reviewed)abstract
- ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10(-8); and LINC00539/ZDHHC20, p = 5.82 x 10(-9). Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p([BI]) = 9.38 x 10(-25); p([SSBI]) = 5.23 x 10(-14) for hypertension), smoking (p([BI]) = 4.4 x 10(-10); p([SSBI]) = 1.2 x 10(-4)), diabetes (p([BI]) = 1.7 x 10(-8); p([SSBI]) = 2.8 x 10(-3)), previous cardiovascular disease (p([BI]) = 1.0 x 10(-18); p([SSBI]) = 2.3 x 10(-7)), stroke (p([BI]) = 3.9 x 10(-69); p([SSBI]) = 3.2 x 10(-24)), and MRI-defined white matter hyperintensity burden (p([BI]) = 1.43 x 10(-157); p([SSBI]) = 3.16 x 10(-106)), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
|
|
| 17. |
|
|
| 18. |
- Postmus, I., et al.
(author)
-
Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- 2016
-
In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:12, s. 835-45
-
Journal article (peer-reviewed)abstract
- Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1x10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Conclusions Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
|
|
| 19. |
- Underwood, J, et al.
(author)
-
Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
- 2019
-
In: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
-
Journal article (peer-reviewed)abstract
- BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
|
|
| 20. |
- Palmese, A., et al.
(author)
-
Stellar mass as a galaxy cluster mass proxy : application to the Dark Energy Survey redMaPPer clusters
- 2020
-
In: \mnras. - : Oxford University Press (OUP). ; 493:4, s. 4591-4606
-
Journal article (peer-reviewed)abstract
- We introduce a galaxy cluster mass observable, μ⋆, based on the stellar masses of cluster members, and we present results for the Dark Energy Survey (DES) Year 1 (Y1) observations. Stellar masses are computed using a Bayesian model averaging method, and are validated for DES data using simulations and COSMOS data. We show that μ⋆ works as a promising mass proxy by comparing our predictions to X-ray measurements. We measure the X-ray temperature–μ⋆ relation for a total of 129 clusters matched between the wide-field DES Y1 redMaPPer catalogue and Chandra and XMM archival observations, spanning the redshift range 0.1 < z < 0.7. For a scaling relation that is linear in logarithmic space, we find a slope of α = 0.488 ± 0.043 and a scatter in the X-ray temperature at fixed μ⋆ of σlnTX|μ⋆=0.266+0.019−0.020 for the joint sample. By using the halo mass scaling relations of the X-ray temperature from the Weighing the Giants program, we further derive the μ⋆-conditioned scatter in mass, finding σlnM|μ⋆=0.26+0.15−0.10. These results are competitive with well-established cluster mass proxies used for cosmological analyses, showing that μ⋆ can be used as a reliable and physically motivated mass proxy to derive cosmological constraints.
|
|
| 21. |
- Patel, Riyaz S., et al.
(author)
-
Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
-
In: Circulation. - 2574-8300. ; 12:4
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
|
|
| 22. |
- Ponnath, L., et al.
(author)
-
Measurement of nuclear interaction cross sections towards neutron-skin thickness determination
- 2024
-
In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 855
-
Journal article (peer-reviewed)abstract
- The accuracy of reaction theories used to extract properties of exotic nuclei from scattering experiments is often unknown or not quantified, but of utmost importance when, e.g., constraining the equation of state of asymmetric nuclear matter from observables as the neutron-skin thickness. In order to test the Glauber multiple-scattering model, the total interaction cross section of [Formula presented] on carbon targets was measured at initial beam energies of 400, 550, 650, 800, and 1000 MeV/nucleon. The measurements were performed during the first experiment of the newly constructed R3B (Reaction with Relativistic Radioactive Beams) experiment after the start of FAIR Phase-0 at the GSI/FAIR facility with beam energies of 400, 550, 650, 800, and 1000 MeV/nucleon. The combination of the large-acceptance dipole magnet GLAD and a newly designed and highly efficient Time-of-Flight detector enabled a precise transmission measurement with several target thicknesses for each initial beam energy with an experimental uncertainty of ±0.4%. A comparison with the Glauber model revealed a discrepancy of around 3.1% at higher beam energies, which will serve as a crucial baseline for the model-dependent uncertainty in future fragmentation experiments.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Farahi, A., et al.
(author)
-
Mass variance from archival X-ray properties of Dark Energy Survey Year-1 galaxy clusters
- 2019
-
In: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 490:3, s. 3341-3354
-
Journal article (peer-reviewed)abstract
- Using archival X-ray observations and a lognormal population model, we estimate constraints on the intrinsic scatter in halo mass at fixed optical richness for a galaxy cluster sample identified in Dark Energy Survey Year-One (DES-Y1) data with the redMaPPer algorithm. We examine the scaling behaviour of X-ray temperatures, T-X, with optical richness, lambda(RM), for clusters in the redshift range 0.2 < z < 0.7. X-ray temperatures are obtained from Chandra and XMM observations for 58 and 110 redMaPPer systems, respectively. Despite non-uniform sky coverage, the T-X measurements are > 50 per cent complete for clusters with lambda(RM) > 130. Regression analysis on the two samples produces consistent posterior scaling parameters, from which we derive a combined constraint on the residual scatter, sigma(ln) (T) (vertical bar) (lambda) = 0.275 +/- 0.019. Joined with constraints for T-X scaling with halo mass from the Weighing the Giants program and richness-temperature covariance estimates from the LoCuSS sample, we derive the richness-conditioned scatter in mass, sigma(ln) (M) (vertical bar) (lambda) = 0.30 +/- 0.04((stat)) +/- 0.09((sys)), at an optical richness of approximately 100. Uncertainties in external parameters, particularly the slope and variance of the T-X-mass relation and the covariance of T-X and lambda(RM) at fixed mass, dominate the systematic error. The 95 per cent confidence region from joint sample analysis is relatively broad, sigma(ln) (M) (vertical bar) (lambda) is an element of [0.14, 0.55], or a factor 10 in variance.
|
|
| 26. |
- Patel, Riyaz S., et al.
(author)
-
Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
-
In: Circulation. - 2574-8300. ; 12:4
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Graña-González, A., et al.
(author)
-
Quasi-free (p,2p) reactions in inverse kinematics for studying the fission yield dependence on temperature
- 2023
-
In: FAIR next generation scientists - 7th Edition Workshop : FAIRness2022 - FAIRness2022. - 1824-8039. ; 419
-
Conference paper (peer-reviewed)abstract
- Despite the recent experimental and theoretical progress in the investigation of the nuclear fission process, a complete description still represents a challenge in nuclear physics because it is a very complex dynamical process, whose description involves the coupling between intrinsic and collective degrees of freedom, as well as different quantum-mechanical phenomena. To improve on the existing data on nuclear fission, we produce fission reactions of heavy nuclei in inverse kinematics by using quasi-free (p,2p) scattering, which induce fission through particle-hole excitations that can range from few to ten's of MeV. The measurement of the four-momenta of the two outgoing protons allows to reconstruct the excitation energy of the fissioning compound nucleus and therefore to study the evolution of the fission yields with temperature. The realization of this kind of experiment requires a complex experimental setup, providing full isotopic identification of both fission fragments and an accurate measurement of the momenta of the two outgoing protons. This was realized recently at the GSI/FAIR facility and here some preliminary results are presented.
|
|
| 31. |
- Hibar, Derrek P., et al.
(author)
-
Novel genetic loci associated with hippocampal volume
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
|
|
| 32. |
- Wetzell, V, et al.
(author)
-
Velocity dispersions of clusters in the Dark Energy Survey Y3 redMaPPer catalogue
- 2022
-
In: Monthly notices of the Royal Astronomical Society. - : Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 514:4, s. 4696-4717
-
Journal article (peer-reviewed)abstract
- We measure the velocity dispersions of clusters of galaxies selected by the red-sequence Matched-filter Probabilistic Percolation (redMaPPer) algorithm in the first three years of data from the Dark Energy Survey (DES), allowing us to probe cluster selection and richness estimation, λ, in light of cluster dynamics. Our sample consists of 126 clusters with sufficient spectroscopy for individual velocity dispersion estimates. We examine the correlations between cluster velocity dispersion, richness, X-ray temperature, and luminosity, as well as central galaxy velocity offsets. The velocity dispersion–richness relation exhibits a bimodal distribution. The majority of clusters follow scaling relations between velocity dispersion, richness, and X-ray properties similar to those found for previous samples; however, there is a significant population of clusters with velocity dispersions that are high for their richness. These clusters account for roughly 22 per cent of the λ < 70 systems in our sample, but more than half (55 per cent) of λ < 70 clusters at z > 0.5. A couple of these systems are hot and X-ray bright as expected for massive clusters with richnesses that appear to have been underestimated, but most appear to have high velocity dispersions for their X-ray properties likely due to line-of-sight structure. These results suggest that projection effects contribute significantly to redMaPPer selection, particularly at higher redshifts and lower richnesses. The redMaPPer determined richnesses for the velocity dispersion outliers are consistent with their X-ray properties, but several are X-ray undetected and deeper data are needed to understand their nature.
|
|
| 33. |
- Zhang, Y., et al.
(author)
-
Dark Energy Surveyed Year 1 results : calibration of cluster mis-centring in the redMaPPer catalogues
- 2019
-
In: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 487:2, s. 2578-2593
-
Journal article (peer-reviewed)abstract
- The centre determination of a galaxy cluster from an optical cluster finding algorithm can be offset from theoretical prescriptions or N-body definitions of its host halo centre. These offsets impact the recovered cluster statistics, affecting both richness measurements and the weak lensing shear profile around the clusters. This paper models the centring performance of the redMaPPer cluster finding algorithm using archival X-ray observations of redMaPPer-selected clusters. Assuming the X-ray emission peaks as the fiducial halo centres, and through analysing their offsets to the redMaPPer centres, we find that similar to 75 +/- 8 per cent of the redMaPPer clusters are well centred and the mis-centred offset follows a Gamma distribution in normalized, projected distance. These mis-centring offsets cause a systematic underestimation of cluster richness relative to the well-centred clusters, for which we propose a descriptive model. Our results enable the DES Y1 cluster cosmology analysis by characterizing the necessary corrections to both the weak lensing and richness abundance functions of the DES Y1 redMaPPer cluster catalogue.
|
|
| 34. |
- Lihtar, I., et al.
(author)
-
RELATIVISTIC COULOMB EXCITATION OF 124 Sn
- 2024
-
In: Acta Physica Polonica B, Proceedings Supplement. - 1899-2358. ; 17:3
-
Journal article (peer-reviewed)abstract
- The Coulomb excitation of 124, 128, 130, 132, 134Sn isotopes in the electric field of a Pb target have been studied using the R3B setup as a part of the FAIR Phase-0 program. The experiment was motivated by the possibility of using the nuclear dipole response to infer valuable information on the slope of the symmetry energy of the nuclear equation of state. Measurements were performed in inverse kinematics at relativistic energies of 750 MeV/u and 904 MeV/u. The analysis method and preliminary results for the decay channel with a single outgoing neutron for 124Sn are reported.
|
|
| 35. |
|
|
| 36. |
- Rodriguez-Sancheza, J. L., et al.
(author)
-
Comprehensive investigation of fission yields by using spallation- and (p,2p)induced fission reactions in inverse kinematics
- 2023
-
In: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - 2100-014X. ; 284
-
Conference paper (peer-reviewed)abstract
- In the last decades, measurements of spallation, fragmentation and Coulex induced fission reactions in inverse kinematics have provided valuable data to accurately investigate the fission dynamics and nuclear structure at large deformations of a large variety of stable and non -stable heavy nuclei. To go a step further, we propose now to induce fission by the use of quasi -free (p,2p) scattering reactions in inverse kinematics, which allows us to reconstruct the excitation energy of the compound fissioning system by using the four-momenta of the two outgoing protons. Therefore, this new approach might permit to correlate the excitation energy with the charge and mass distributions of the fission fragments and with the fission probabilities, given for the first time direct access to the simultaneous measurement of the fission yield dependence on temperature and fission barrier heights of exotic heavy nuclei, respectively. The first experiment based on this methodology was realized recently at the GM/FAIR facility and a detailed description of the experimental setup is given here.
|
|
| 37. |
- Sachdev, P. S., et al.
(author)
-
STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease
- 2017
-
In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 7, s. 11-23
-
Journal article (peer-reviewed)abstract
- Introduction The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Methods Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Results Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3months to 21years. Discussion Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes. © 2016 The Authors
|
|
| 38. |
- Zhang, Y., et al.
(author)
-
Galaxies in X-ray selected clusters and groups in Dark Energy Survey data - II. Hierarchical Bayesian modelling of the red-sequence galaxy luminosity function
- 2019
-
In: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 488:1, s. 1-17
-
Journal article (peer-reviewed)abstract
- Using similar to 100 X-ray selected clusters in the Dark Energy Survey Science Verification data, we constrain the luminosity function ( LF) of cluster red-sequence galaxies as a function of redshift. This is the first homogeneous optical/X-ray sample large enough to constrain the evolution of the LF simultaneously in redshift ( 0.1 < z < 1.05) and cluster mass ( 13.5 <= log(10)( M-200crit) similar to< 15.0). We pay particular attention to completeness issues and the detection limit of the galaxy sample. We then apply a hierarchical Bayesian model to fit the cluster galaxy LFs via a Schechter function, including its characteristic break ( m*) to a faint end power-law slope ( alpha). Our method enables us to avoid known issues in similar analyses based on stacking or binning the clusters. We find weak and statistically insignificant (similar to 1.9 sigma) evolution in the faint end slope alpha versus redshift. We also find no dependence in alpha or m* with the X-ray inferred cluster masses. However, the amplitude of the LF as a function of cluster mass is constrained to similar to 20 per cent precision. As a by-product of our algorithm, we utilize the correlation between the LF and cluster mass to provide an improved estimate of the individual cluster masses as well as the scatter in true mass given the X-ray inferred masses. This technique can be applied to a larger sample of X-ray or optically selected clusters from the Dark Energy Survey, significantly improving the sensitivity of the analysis.
|
|
| 39. |
|
|
| 40. |
- Evangelou, Evangelos, et al.
(author)
-
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
-
Journal article (peer-reviewed)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
|
|
| 41. |
- Wain, Louise V., et al.
(author)
-
Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
-
In: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
-
Journal article (peer-reviewed)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Mehrtens, N., et al.
(author)
-
The XMM Cluster Survey : the halo occupation number of BOSS galaxies in X-ray clusters
- 2016
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 463:2, s. 1929-1943
-
Journal article (peer-reviewed)abstract
- We present a direct measurement of the mean halo occupation distribution (HOD) of galaxies taken from the eleventh data release (DR11) of the Sloan Digital Sky Survey-III Baryon Oscillation Spectroscopic Survey (BOSS). The HOD of BOSS low-redshift (LOWZ: 0.2 < z < 0.4) and Constant-Mass (CMASS: 0.43 < z < 0.7) galaxies is inferred via their association with the dark matter haloes of 174 X-ray-selected galaxy clusters drawn from the XMM Cluster Survey (XCS). Halo masses are determined for each galaxy cluster based on X-ray temperature measurements, and range between log10(M180/M⊙) = 13 and 15. Our directly measured HODs are consistent with the HOD-model fits inferred via the galaxy-clustering analyses of Parejko et al. for the BOSS LOWZ sample and White et al. for the BOSS CMASS sample. Under the simplifying assumption that the other parameters that describe the HOD hold the values measured by these authors, we have determined a best-fitting alpha-index of 0.91 ± 0.08 and 1.27−0.04+0.03" role="presentation">1.27+0.03−0.04 for the CMASS and LOWZ HOD, respectively. These alpha-index values are consistent with those measured by White et al. and Parejko et al. In summary, our study provides independent support for the HOD models assumed during the development of the BOSS mock-galaxy catalogues that have subsequently been used to derive BOSS cosmological constraints.
|
|
| 45. |
|
|
| 46. |
- Pennells, Lisa, et al.
(author)
-
Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
-
In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
-
Journal article (peer-reviewed)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
|
|
| 47. |
- Schunk, Stefan J., et al.
(author)
-
Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
- 2021
-
In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756
-
Journal article (peer-reviewed)abstract
- AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
- Mehrtens, Nicola, et al.
(author)
-
The XMM Cluster Survey : optical analysis methodology and the first data release
- 2012
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 423:2, s. 1024-1052
-
Journal article (peer-reviewed)abstract
- The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMMNewton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we present the first data release from the XMM Cluster Survey (XCS-DR1). This consists of 503 optically confirmed, serendipitously detected, X-ray clusters. Of these clusters, 256 are new to the literature and 357 are new X-ray discoveries. We present 463 clusters with a redshift estimate (0.06 < z < 1.46), including 261 clusters with spectroscopic redshifts. The remainder have photometric redshifts. In addition, we have measured X-ray temperatures (TX) for 401 clusters (0.4 < TX < 14.7 keV). We highlight seven interesting subsamples of XCS-DR1 clusters: (i) 10 clusters at high redshift (z > 1.0, including a new spectroscopically confirmed cluster at z= 1.01); (ii) 66 clusters with high TX (>5 keV); (iii) 130 clusters/groups with low TX (<2 keV); (iv) 27 clusters with measured TX values in the Sloan Digital Sky Survey (SDSS) Stripe 82 co-add region; (v) 77 clusters with measured TX values in the Dark Energy Survey region; (vi) 40 clusters detected with sufficient counts to permit mass measurements (under the assumption of hydrostatic equilibrium); (vii) 104 clusters that can be used for applications such as the derivation of cosmological parameters and the measurement of cluster scaling relations. The X-ray analysis methodology used to construct and analyse the XCS-DR1 cluster sample has been presented in a companion paper, Lloyd-Davies et al.
|
|
