| 1. |
- Jelenkovic, Aline, et al.
(författare)
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Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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| 2. |
- Silventoinen, Karri, et al.
(författare)
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The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
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| 3. |
- Pirzkal, Norbert, et al.
(författare)
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A Two-dimensional Spectroscopic Study of Emission-line Galaxies in the Faint Infrared Grism Survey (FIGS). I. Detection Method and Catalog
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 868:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the results from the application of a two-dimensional emission line detection method, EMission-line two-Dimensional (EM2D), to the near-infrared G102 grism observations obtained with the Wide-Field Camera 3 (WFC3) as part of the Cycle 22 Hubble Space Telescope Treasury Program: the Faint Infrared Grism Survey (FIGS). Using the EM2D method, we have assembled a catalog of emission line galaxies (ELGs) with resolved star formation from each of the four FIGS fields. Not only can one better assess the global properties of ELGs, but the EM2D method allows for the analysis and improved study of the individual emission-line region within each galaxy. This paper includes a description of the methodology, advantages, and the first results of the EM2D method applied to ELGs in FIGS. The advantage of 2D emission line measurements includes significant improvement of galaxy redshift measurements, approaching the level of accuracy seen in high-spectral-resolution data, but with greater efficiency; and the ability to identify and measure the properties of multiple sites of star formation and over scales of similar to 1 kpc within individual galaxies out to z similar to 4. The EM2D method also significantly improves the reliability of high-redshift (z similar to 7) Ly alpha detections. Coupled with the wide field of view and high efficiency of space-based grism observations, EM2D provides a noteworthy improvement on the physical parameters that can be extracted from grism observations.
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| 4. |
- Pirzkal, Norbert, et al.
(författare)
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FIGS-Faint Infrared Grism Survey : Description and Data Reduction
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 846:1
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Tidskriftsartikel (refereegranskat)abstract
- The Faint Infrared Grism Survey (FIGS) is a deep Hubble Space Telescope (HST) WFC3/IR (Wide Field Camera 3 Infrared) slitless spectroscopic survey of four deep fields. Two fields are located in the Great Observatories Origins Deep Survey-North (GOODS-N) area and two fields are located in the Great Observatories Origins Deep Survey-South (GOODS-S) area. One of the southern fields selected is the Hubble Ultra Deep Field. Each of these four fields were observed using the WFC3/G102 grism (0.8 mu m-1.15 mu m continuous coverage) with a total exposure time of 40 orbits (approximate to 100 kilo-seconds) per field. This reaches a 3 sigma continuum depth of approximate to 26 AB magnitudes and probes emission lines to similar to 10(-17) erg s(-1) cm(-2). This paper details the four FIGS fields and the overall observational strategy of the project. A detailed description of the Simulation Based Extraction (SBE) method used to extract and combine over 10,000 spectra of over 2000 distinct sources brighter than m(F105W) = 26.5 mag is provided. High fidelity simulations of the observations is shown to significantly improve the background subtraction process, the spectral contamination estimates, and the final flux calibration. This allows for the combination of multiple spectra to produce a final high quality, deep, 1D spectra for each object in the survey.
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| 5. |
- Larson, Rebecca L., et al.
(författare)
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Discovery of a z=7.452 High Equivalent Width Ly alpha Emitter from the Hubble Space Telescope Faint Infrared Grism Survey
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 858:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of an unbiased search for Ly alpha emission from continuum-selected 5.6 < z < 8.7 galaxies. Our data set consists of 160 orbits of G102 slitless grism spectroscopy obtained with the Hubble Space Telescope (HST)/WFC3 as part of the Faint Infrared Grism Survey (FIGS; PI: Malhotra), which obtains deep slitless spectra of all sources in four fields, and was designed to minimize contamination in observations of previously identified high-redshift galaxy candidates. The FIGS data can potentially spectroscopically confirm the redshifts of galaxies, and as Ly alpha emission is resonantly scattered by neutral gas, FIGS can also constrain the ionization state of the intergalactic medium during the epoch of reionization. These data have sufficient depth to detect Ly alpha emission in this epoch, as Tilvi et al. have published the FIGS detection of previously known Ly alpha emission at z = 7.51. The FIGS data use five separate roll angles of HST to mitigate the contamination by nearby galaxies. We created a method that accounts for and removes the contamination from surrounding galaxies and also removes any dispersed continuum light from each individual spectrum. We searched for significant (>4 sigma) emission lines using two different automated detection methods, free of any visual inspection biases. Applying these methods on photometrically selected high-redshift candidates between 5.6 < z < 8.7, we find two emission lines, one previously published by Tilvi et al., (2016) and a new line at 1.028 mu m, which we identify as Ly alpha at z = 7.452 +/- 0.003. This newly spectroscopically confirmed galaxy has the highest Ly alpha rest-frame equivalent width (EWLy alpha) yet published at z > 7 (140.3 +/- 19.0 ångström).
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| 6. |
- Surendran, Praveen, et al.
(författare)
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Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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| 7. |
- Thomassen, Mads, et al.
(författare)
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Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants : Application of a points-based ACMG/AMP approach
- 2022
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 43:12, s. 1921-1944
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Tidskriftsartikel (refereegranskat)abstract
- Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.
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| 8. |
- Buus, Terkild Brink, et al.
(författare)
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Single-cell heterogeneity in Sézary syndrome
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
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Tidskriftsartikel (refereegranskat)abstract
- Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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| 9. |
- Christensen, Lise Lotte, et al.
(författare)
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The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population
- 2008
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 9, s. 52-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mutations in the mismatch repair genes hMLH1 and hMSH2 predispose to hereditary non-polyposis colorectal cancer (HNPCC). Genetic screening of more than 350 Danish patients with colorectal cancer (CRC) has led to the identification of several new genetic variants (e.g. missense, silent and non-coding) in hMLH1 and hMSH2. The aim of the present study was to investigate the frequency of these variants in hMLH1 and hMSH2 in Danish patients with sporadic colorectal cancer and in the healthy background population. The purpose was to reveal if any of the common variants lead to increased susceptibility to colorectal cancer. METHODS: Associations between genetic variants in hMLH1 and hMSH2 and sporadic colorectal cancer were evaluated using a case-cohort design. The genotyping was performed on DNA isolated from blood from the 380 cases with sporadic colorectal cancer and a sub-cohort of 770 individuals. The DNA samples were analyzed using Single Base Extension (SBE) Tag-arrays. A Bonferroni corrected Fisher exact test was used to test for association between the genotypes of each variant and colorectal cancer. Linkage disequilibrium (LD) was investigated using HaploView (v3.31). RESULTS: Heterozygous and homozygous changes were detected in 13 of 35 analyzed variants. Two variants showed a borderline association with colorectal cancer, whereas the remaining variants demonstrated no association. Furthermore, the genomic regions covering hMLH1 and hMSH2 displayed high linkage disequilibrium in the Danish population. Twenty-two variants were neither detected in the cases with sporadic colorectal cancer nor in the sub-cohort. Some of these rare variants have been classified either as pathogenic mutations or as neutral variants in other populations and some are unclassified Danish variants. CONCLUSION: None of the variants in hMLH1 and hMSH2 analyzed in the present study were highly associated with colorectal cancer in the Danish population. High linkage disequilibrium in the genomic regions covering hMLH1 and hMSH2, indicate that common genetic variants in the two genes in general are not involved in the development of sporadic colorectal cancer. Nevertheless, some of the rare unclassified variants in hMLH1 and hMSH2 might be involved in the development of colorectal cancer in the families where they were originally identified.
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| 10. |
- Ferreras, Ignacio, et al.
(författare)
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FIGS : spectral fitting constraints on the star formation history of massive galaxies since the cosmic noon
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 486:1, s. 1358-1376
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Tidskriftsartikel (refereegranskat)abstract
- We constrain the stellar population properties of a sample of 52 massive galaxies - with stellar mass log (M-s/M-circle dot) greater than or similar to 10.5 - over the redshift range 0.5 < z < 2 by use of observer-frame optical and near-infrared slitless spectra from Hubble Space Telescope's ACS and WFC3 grisms. The deep exposures (similar to 100 ks) allow us to target individual spectra of massive galaxies to F160W = 22.5AB. Our spectral fitting approach uses a set of six base models adapted to the redshift and spectral resolution of each observation, and fits the weights of the base models, including potential dust attenuation, via a Markov Chain Monte Carlo method. Our sample comprises a mixed distribution of quiescent (19) and star-forming galaxies (33). We quantify the width of the age distribution (Delta t) that is found to dominate the variance of the retrieved parameters according to principal component analysis. The population parameters follow the expected trend towards older ages with increasing mass, and Delta t appears to weakly anticorrelate with stellar mass, suggesting a more efficient star formation at the massive end. As expected, the redshift dependence of the relative stellar age (measured in units of the age of the Universe at the source) in the quiescent sample rejects the hypothesis of a single burst (aka monolithic collapse). Radial colour gradients within each galaxy are also explored, finding a wider scatter in the star-forming subsample, but no conclusive trend with respect to the population parameters.
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| 11. |
- Fleischer, Thomas, et al.
(författare)
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Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:8, s. 435-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Results: We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals that DNA methylation profiles of DCIS are radically altered compared to normal breast tissue, involving more than 5,000 genes. Changes between DCIS and invasive breast carcinoma involve around 1,000 genes. In tumors, DNA methylation is associated with gene expression of almost 3,000 genes, including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs is associated with survival of breast cancer patients with invasive tumors, as well as with survival of patients with DCIS and mixed lesions of DCIS and invasive breast carcinoma. Conclusions: This work demonstrates that changes in the epigenome occur early in the neoplastic progression, provides evidence for the possible utilization of DNA methylation-based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis.
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| 12. |
- Pharo, John, et al.
(författare)
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Emission-line Metallicities from the Faint Infrared Grism Survey and VLT/MUSE
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 874:2
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Tidskriftsartikel (refereegranskat)abstract
- We derive direct-measurement gas-phase metallicities of 7.4 < 12 + log (O/H) < 8.4 for 14 low-mass emissionline galaxies at 0.3 < z < 0.8 identified in the Faint Infrared Grism Survey. We use deep slitless G102 grism spectroscopy of the Hubble Ultra Deep Field, dispersing light from all objects in the field at wavelengths between 0.85 and 1.15 mu m. We run an automatic search routine on these spectra to robustly identify 71 emission-line sources, using archival data from Very Large Telescope (VLT)/Multi-Unit Spectroscopic Explorer (MUSE) to measure additional lines and confirm redshifts. We identify 14 objects with 0.3 < z < 0.8 with measurable [O Iota Iota Iota] lambda 4363 angstrom emission lines in matching VLT/MUSE spectra. For these galaxies, we derive direct electron-temperature gas-phase metallicities with a range of 7.4 < 12 + log (O/H) < 8.4. With matching stellar masses in the range of 10(7.9) M-circle dot < M* < 10(10.4) M-circle dot, we construct a mass-metallicity (MZ) relation and find that the relation is offset to lower metallicities compared to metallicities derived from alternative methods (e.g., R-23,O3N2, N2O2) and continuum selected samples. Using star formation rates derived from the H alpha emission line, we calculate our galaxies' position on the Fundamental Metallicity Relation, where we also find an offset toward lower metallicities. This demonstrates that this emission-line-selected sample probes objects of low stellar masses but even lower metallicities than many comparable surveys. We detect a trend suggesting galaxies with higher Specific Star Formation (SSFR) are more likely to have lower metallicity. This could be due to cold accretion of metal-poor gas that drives star formation, or could be because outflows of metal-rich stellar winds and SNe ejecta are more common in galaxies with higher SSFR.
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