| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 3. |
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| 4. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 5. |
- van Kuilenburg, Andre B. P., et al.
(författare)
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Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 380:15, s. 1433-1441
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Tidskriftsartikel (refereegranskat)abstract
- We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5′ untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing.
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| 6. |
- Kessler, Richard, et al.
(författare)
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First-Year Sloan Digital Sky Survey-II Supernova Results : Hubble Diagram and Cosmological Parameters
- 2009
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 185:1, s. 32-84
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the Hubble diagram for 103 Type Ia supernovae (SNe) with redshifts 0.04 < z < 0.42, discovered during the first season (Fall 2005) of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. These data fill in the redshift "desert" between low- and high-redshift SN Ia surveys. Within the framework of the MLCS2K2 light-curve fitting method, we use the SDSS-II SN sample to infer the mean reddening parameter for host galaxies, RV = 2.18 ± 0.14stat ± 0.48syst, and find that the intrinsic distribution of host-galaxy extinction is well fitted by an exponential function, P(AV ) = exp(-AV /τV), with τV = 0.334 ± 0.088 mag. We combine the SDSS-II measurements with new distance estimates for published SN data from the ESSENCE survey, the Supernova Legacy Survey (SNLS), the Hubble Space Telescope (HST), and a compilation of Nearby SN Ia measurements. A new feature in our analysis is the use of detailed Monte Carlo simulations of all surveys to account for selection biases, including those from spectroscopic targeting. Combining the SN Hubble diagram with measurements of baryon acoustic oscillations from the SDSS Luminous Red Galaxy sample and with cosmic microwave background temperature anisotropy measurements from the Wilkinson Microwave Anisotropy Probe, we estimate the cosmological parameters w and ΩM, assuming a spatially flat cosmological model (FwCDM) with constant dark energy equation of state parameter, w. We also consider constraints upon ΩM and ΩΛ for a cosmological constant model (ΛCDM) with w = -1 and non-zero spatial curvature. For the FwCDM model and the combined sample of 288 SNe Ia, we find w = -0.76 ± 0.07(stat) ± 0.11(syst), ΩM = 0.307 ± 0.019(stat) ± 0.023(syst) using MLCS2K2 and w = -0.96 ± 0.06(stat) ± 0.12(syst), ΩM = 0.265 ± 0.016(stat) ± 0.025(syst) using the SALT-II fitter. We trace the discrepancy between these results to a difference in the rest-frame UV model combined with a different luminosity correction from color variations; these differences mostly affect the distance estimates for the SNLS and HST SNe. We present detailed discussions of systematic errors for both light-curve methods and find that they both show data-model discrepancies in rest-frame U band. For the SALT-II approach, we also see strong evidence for redshift-dependence of the color-luminosity parameter (β). Restricting the analysis to the 136 SNe Ia in the Nearby+SDSS-II samples, we find much better agreement between the two analysis methods but with larger uncertainties: w = -0.92 ± 0.13(stat)+0.10 -0.33(syst) for MLCS2K2 and w = -0.92 ± 0.11(stat)+0.07 -0.15 (syst) for SALT-II.
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| 7. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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| 8. |
- Sako, Masao, et al.
(författare)
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The Data Release of the Sloan Digital Sky Survey-II Supernova Survey
- 2018
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 130:988
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the data release of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey conducted between 2005 and 2007. Light curves, spectra, classifications, and ancillary data are presented for 10,258 variable and transient sources discovered through repeat ugriz imaging of SDSS Stripe 82, a 300 deg(2) area along the celestial equator. This data release is comprised of all transient sources brighter than r similar or equal to 22.5 mag with no history of variability prior to 2004. Dedicated spectroscopic observations were performed on a subset of 889 transients, as well as spectra for thousands of transient host galaxies using the SDSS-III BOSS spectrographs. Photometric classifications are provided for the candidates with good multi-color light curves that were not observed spectroscopically, using host galaxy redshift information when available. From these observations, 4607 transients are either spectroscopically confirmed, or likely to be, supernovae, making this the largest sample of supernova candidates ever compiled. We present a new method for SN host-galaxy identification and derive host-galaxy properties including stellar masses, star formation rates, and the average stellar population ages from our SDSS multi-band photometry. We derive SALT2 distance moduli for a total of 1364 SN. Ia with spectroscopic redshifts as well as photometric redshifts for a further 624 purely photometric SN. Ia candidates. Using the spectroscopically confirmed subset of the three-year SDSS-II SN. Ia sample and assuming a flat.CDM cosmology, we determine Omega(M) = 0.315 +/- 0.093 (statistical error only) and detect a non-zero cosmological constant at 5.7 sigma.
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| 9. |
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| 10. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 11. |
- Campbell, Heather, et al.
(författare)
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COSMOLOGY WITH PHOTOMETRICALLY CLASSIFIED TYPE Ia SUPERNOVAE FROM THE SDSS-II SUPERNOVA SURVEY
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 763:2, s. 88-
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Tidskriftsartikel (refereegranskat)abstract
- We present the cosmological analysis of 752 photometrically classified Type Ia Supernovae (SNe Ia) obtained from the full Sloan Digital Sky Survey II (SDSS-II) Supernova (SN) Survey, supplemented with host-galaxy spectroscopy from the SDSS-III Baryon Oscillation Spectroscopic Survey. Our photometric-classification method is based on the SN classification technique of Sako et al., aided by host-galaxy redshifts (0.05 < z < 0.55). SuperNova ANAlysis simulations of our methodology estimate that we have an SN Ia classification efficiency of 70.8%, with only 3.9% contamination from core-collapse (non-Ia) SNe. We demonstrate that this level of contamination has no effect on our cosmological constraints. We quantify and correct for our selection effects (e. g., Malmquist bias) using simulations. When fitting to a flat.CDM cosmological model, we find that our photometric sample alone gives Omega(m) = 0.24(-0.05)(+0.07) (statistical errors only). If we relax the constraint on flatness, then our sample provides competitive joint statistical constraints on Omega(m) and Omega(Lambda), comparable to those derived from the spectroscopically confirmed Three-year Supernova Legacy Survey (SNLS3). Using only our data, the statistics-only result favors an accelerating universe at 99.96% confidence. Assuming a constant wCDM cosmological model, and combining with H-0, cosmic microwave background, and luminous red galaxy data, we obtain w = -0.96(-0.10)(+0.10), Omega(m) = 0.29(-0.02)(+0.02), and Omega(k) = 0.00(-0.02)(+0.03)(statistical errors only), which is competitive with similar spectroscopically confirmed SNe Ia analyses. Overall this comparison is reassuring, considering the lower redshift leverage of the SDSS-II SN sample (z < 0.55) and the lack of spectroscopic confirmation used herein. These results demonstrate the potential of photometrically classified SN Ia samples in improving cosmological constraints.
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| 12. |
- Davis, Tamara M., et al.
(författare)
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The Effect of Peculiar Velocities on Supernova Cosmology
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 741, s. 67-
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Tidskriftsartikel (refereegranskat)abstract
- We analyze the effect that peculiar velocities have on the cosmological inferences we make using luminosity distance indicators, such as Type Ia supernovae. In particular we study the corrections required to account for (1) our own motion, (2) correlations in galaxy motions, and (3) a possible local under- or overdensity. For all of these effects we present a case study showing the impact on the cosmology derived by the Sloan Digital Sky Survey-II Supernova Survey (SDSS-II SN Survey). Correcting supernova (SN) redshifts for the cosmic microwave background (CMB) dipole slightly overcorrects nearby SNe that share some of our local motion. We show that while neglecting the CMB dipole would cause a shift in the derived equation of state of Δw ~ 0.04 (at fixed Ω m ), the additional local-motion correction is currently negligible (Δw <~ 0.01). We then demonstrate a covariance-matrix approach to statistically account for correlated peculiar velocities. This down-weights nearby SNe and effectively acts as a graduated version of the usual sharp low-redshift cut. Neglecting coherent velocities in the current sample causes a systematic shift of Δw ~ 0.02. This will therefore have to be considered carefully when future surveys aim for percent-level accuracy and we recommend our statistical approach to down-weighting peculiar velocities as a more robust option than a sharp low-redshift cut.
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| 13. |
- Fairfield, Heather, et al.
(författare)
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Mutation discovery in mice by whole exome sequencing
- 2011
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 12:9, s. R86-
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Tidskriftsartikel (refereegranskat)abstract
- We report the development and optimization of reagents for in-solution, hybridization-based capture of the mouse exome. By validating this approach in a multiple inbred strains and in novel mutant strains, we show that whole exome sequencing is a robust approach for discovery of putative mutations, irrespective of strain background. We found strong candidate mutations for the majority of mutant exomes sequenced, including new models of orofacial clefting, urogenital dysmorphology, kyphosis and autoimmune hepatitis.
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| 14. |
- Mansoor, Rashid, et al.
(författare)
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Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
- 2022
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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| 15. |
- Morokuma, Tomoki, et al.
(författare)
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Kiso Supernova Survey (KISS) : Survey strategy
- 2014
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Ingår i: Nippon Tenmon Gakkai obun kenkyu hokoku. - : Oxford University Press (OUP). - 0004-6264. ; 66:6
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Tidskriftsartikel (refereegranskat)abstract
- lThe Kiso Supernova Survey (KISS) is a high-cadence optical wide-field supernova (SN) survey. The primary goal of the survey is to catch the very early light of a SN, during the shock breakout phase. Detection of SN shock breakouts combined with multi-band photometry obtained with other facilities would provide detailed physical information on the progenitor stars of SNe. The survey is performed using a 2 degrees.2 x 2 degrees.2 field-of-view instrument on the 1.05-m Kiso Schmidt telescope, the Kiso Wide Field Camera (KWFC). We take a 3-min exposure in g-band once every hour in our survey, reaching magnitude g similar to 20-21. About 100 nights of telescope time per year have been spent on the survey since 2012 April. The number of the shock breakout detections is estimated to be of the order of 1 during our three-year project. This paper summarizes the KISS project including the KWFC observing setup, the survey strategy, the data reduction system, and CBET-reported SNe discovered so far by KISS.
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| 16. |
- Tanaka, Masaomi, et al.
(författare)
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DISCOVERY OF DRAMATIC OPTICAL VARIABILITY IN SDSS J1100+4421 : A PECULIAR RADIO-LOUD NARROW-LINE SEYFERT 1 GALAXY?
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 793:2, s. L26-
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Tidskriftsartikel (refereegranskat)abstract
- We present our discovery of dramatic variability in SDSS J1100+4421 by the high-cadence transient survey Kiso Supernova Survey. The source brightened in the optical by at least a factor of three within about half a day. Spectroscopic observations suggest that this object is likely a narrow-line Seyfert 1 galaxy (NLS1) at z = 0.840, however, with unusually strong narrow emission lines. The estimated black hole mass of similar to 10(7) M-circle dot implies bolometric nuclear luminosity close to the Eddington limit. SDSS J1100+4421 is also extremely radio-loud, with a radio loudness parameter of R similar or equal to 4 x 10(2)-3 x 10(3), which implies the presence of relativistic jets. Rapid and large-amplitude optical variability of the target, reminiscent of that found in a few radio- and gamma-ray-loud NLS1s, is therefore produced most likely in a blazar-like core. The 1.4 GHz radio image of the source shows an extended structure with a linear size of about 100 kpc. If SDSS J1100+4421 is a genuine NLS1, as suggested here, this radio structure would then be the largest ever discovered in this type of active galaxies.
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| 17. |
- Tyrrell, Jessica, et al.
(författare)
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Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.
- 2016
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 315:11, s. 1129-40
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Tidskriftsartikel (refereegranskat)abstract
- Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.Offspring birth weight from 18 studies.Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P=.008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P=7×10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P=1×10(-5)), respectively. A 1-SD (≈4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD (≈7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD (≈10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
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