| 31. |
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| 32. |
- Bishop, D. Timothy, et al.
(författare)
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Genome-wide association study identifies three loci associated with melanoma risk
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:8, s. 920-925
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 x 10(-7). Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 x 10(-27) for rs258322), 11q14-q21 encompassing TYR (P = 2.41 x 10(-14) for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 x 10(-7) for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.
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| 33. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 34. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 35. |
- Tinyanont, S., et al.
(författare)
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Keck Infrared Transient Survey. I. Survey Description and Data Release 1
- 2024
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 136:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the Keck Infrared Transient Survey, a NASA Key Strategic Mission Support program to obtain near-infrared (NIR) spectra of astrophysical transients of all types, and its first data release, consisting of 105 NIR spectra of 50 transients. Such a data set is essential as we enter a new era of IR astronomy with the James Webb Space Telescope (JWST) and the upcoming Nancy Grace Roman Space Telescope (Roman). NIR spectral templates will be essential to search JWST images for stellar explosions of the first stars and to plan an effective Roman SN Ia cosmology survey, both key science objectives for mission success. Between 2022 February and 2023 July, we systematically obtained 274 NIR spectra of 146 astronomical transients, representing a significant increase in the number of available NIR spectra in the literature. Here, we describe the first release of data from the 2022A semester. We systematically observed three samples: a flux-limited sample that includes all transients <17 mag in a red optical band (usually ZTF r or ATLAS o bands); a volume-limited sample including all transients within redshift z < 0.01 (D ≈ 50 Mpc); and an SN Ia sample targeting objects at phases and light-curve parameters that had scant existing NIR data in the literature. The flux-limited sample is 39% complete (60% excluding SNe Ia), while the volume-limited sample is 54% complete and is 79% complete to z = 0.005. Transient classes observed include common Type Ia and core-collapse supernovae, tidal disruption events, luminous red novae, and the newly categorized hydrogen-free/helium-poor interacting Type Icn supernovae. We describe our observing procedures and data reduction using PypeIt, which requires minimal human interaction to ensure reproducibility.
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| 36. |
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| 37. |
- Dellenmark-Blom, Michaela, 1983, et al.
(författare)
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Establishment of a condition-specific quality-of-life questionnaire for children born with esophageal atresia aged 2-7 across 14 countries
- 2023
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Ingår i: Frontiers in Pediatrics. - 2296-2360. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEsophageal atresia (EA) is a rare congenital anomaly characterized by a discontinuity of the esophagus. Following surgical repair, survival rates have improved dramatically the past decenniums and today exceed 90%, but the children commonly present with esophageal and respiratory morbidity. In 2018, a condition-specific quality-of-life questionnaire for children with esophageal atresia (EA) aged 2-7 in Sweden-Germany was finalized (The EA-QOL questionnaire). The study aim was to describe the evaluation of the new translations across 12 new countries in Europe, Asia, Africa, Central-and North America.MethodsFollowing forward-backward translation into the new languages, the 17-item EA-QOL questionnaire was tested in cognitive debriefing interviews with parents of children with EA aged 2-7. Parents rated if each item was easy to understand (clarity) and sensitive to answer (interference with personal integrity). They could skip responding to a non-applicable/problematic item and give open comments. Predefined psychometric criteria were used; item clarity >= 80%/item sensitive to answer <= 20%/item feasibility <= 5% missing item responses. The decision to modify the translation was based on native expert, patient stakeholder, and instrument developer review, and the need for harmonization between translations.ResultsSimilar to findings in the Swedish-German cognitive debriefing, the cross-cultural analysis of input from 116 parents from 12 new countries (4-14 parents, median 9 parents/country) showed that all items in the EA-QOL questionnaire fulfilled the criteria for item clarity >= 80% and sensitive to answer (ranging from 1%-4.5%), although results varied between countries. Four items had missing responses between 5.2% and 13.4%, three within the same domain and were in line with parents' explanations. Poor translations and feasibility were improved.ConclusionsBased on parent input, the collaboration between native experts, patient stakeholders, and instrument developers, a linguistic version of the EA-QOL questionnaire for children aged 2-7 for use in and across 14 countries has been established. These efforts have set the conditions for a cross-cultural field test of the EA-QOL questionnaire and will open the doors for a new chapter in outcome research, registries, and clinical practice concerning children with EA. In the long-term, this will help increase knowledge of the disease's burden, promote patient-centeredness, exchange of information between nations, and strengthen evidence-based treatments for children born with EA.
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| 38. |
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| 40. |
- Morello, Giuseppe, 1989, et al.
(författare)
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TOI-1442 b and TOI-2445 b: Two potentially rocky ultra-short period planets around M dwarfs
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 673
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Tidskriftsartikel (refereegranskat)abstract
- Context. Exoplanets with orbital periods of less than one day are known as ultra-short period (USP) planets. They are relatively rare products of planetary formation and evolution processes, but especially favourable for characterisation with current planet detection methods. At the time of writing, 125 USP planets have already been confirmed. Aims. Our aim is to validate the planetary nature of two new transiting planet candidates around M dwarfs announced by the NASA Transiting Exoplanet Survey Satellite (TESS), registered as TESS Objects of Interest (TOIs) TOI-1442.01 and TOI-2445.01. Methods. We used TESS data, ground-based photometric light curves, and Subaru/IRD spectrograph radial velocity (RV) measurements to validate both planetary candidates and to establish their physical properties. Results. TOI-1442 b is a validated exoplanet with an orbital period of P = 0.4090682 ± 0.0000004 day, a radius of Rp = 1.15 ± 0.06 R☉, and equilibrium temperature of Tp,eq = 1357+−4942 K. TOI-2445 b is also validated with an orbital period of P = 0.3711286 ± 0.0000004 day, a radius of Rp = 1.33 ± 0.09 R☉, and equilibrium temperature of Tp,eq = 1330+−6156 K. Their physical properties align with current empirical trends and formation theories of USP planets. Based on the RV measurements, we set 3σ upper mass limits of 8 M☉ and 20 M☉, thus confirming the non-stellar, sub-Jovian nature of both transiting objects. More RV measurements will be needed to constrain the planetary masses and mean densities, and the predicted presence of outer planetary companions. These targets extend the small sample of USP planets orbiting around M dwarfs up to 21 members. They are also among the 20 most suitable terrestrial planets for atmospheric characterisation via secondary eclipse with the James Webb Space Telescope, according to a widespread emission spectroscopy metric.
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