| 11. |
- Eckel-Passow, Jeanette E., et al.
(author)
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Using germline variants to estimate glioma and subtype risks
- 2019
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In: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 21:4, s. 451-461
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Journal article (peer-reviewed)abstract
- Background: Twenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes.Methods: Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray.Results: Patients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85.Conclusions: These results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.
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| 12. |
- Kaput, J, et al.
(author)
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The case for strategic international alliances to harness nutritional genomics for public and personal health
- 2005
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In: The British journal of nutrition. - : Cambridge University Press (CUP). - 0007-1145 .- 1475-2662. ; 94:5, s. 623-632
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Journal article (peer-reviewed)abstract
- Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
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| 13. |
- Machiela, Mitchell J, et al.
(author)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 14. |
- Marcelli, L., et al.
(author)
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Integration, qualification, and launch of the Mini-EUSO telescope on board the ISS
- 2023
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In: Rendiconti Lincei SCIENZE FISICHE E NATURALI. - : Springer Nature. - 2037-4631 .- 1720-0776. ; 34:1, s. 23-35
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Journal article (peer-reviewed)abstract
- Mini-EUSO is a high-sensitivity imaging telescope that observes the Earth from the ISS in the near ultraviolet band (290÷ 430 nm), through the nadir-facing, UV-transparent window in the Russian Zvezda module. The instrument, launched in 2019, has a field of view of 44∘, a spatial resolution on the Earth’s surface of 6.3 km and a temporal sampling rate of 2.5 microseconds. Thanks to its triggering and on-board processing, the telescope is capable of detecting UV emissions of cosmic, atmospheric, and terrestrial origin on different time scales, from a few microseconds up to tens of milliseconds. The optics is composed of two Fresnel lenses focusing light onto an array of 36 Hamamatsu Multi-Anode PhotoMultiplier Tubes, for a total of 2304 pixels. The telescope also contains two cameras in the near-infrared and visible, an 8-by-8 array of Silicon-PhotoMultipliers and a series of UV sensors to manage night-day transitions. The scientific objectives range from the observation of atmospheric phenomena [lightning, Transient Luminous Events (TLEs), ELVES], the study of meteoroids, the search of interstellar meteoroids and strange quark matter, mapping of the Earth’s nocturnal emissions in the ultraviolet range, and the search of cosmic rays with energy above 1021 eV. The instrument has been integrated and qualified in 2019, with the final tests in Baikonur prior to its launch. Operations involve periodic installation in the Zvezda module of the station with observations during the crew night time, with periodic downlink of data samples, with the full data being sent to the ground via pouches containing the data disks. Mission planning involves the selection of the optimal orbits to maximize the scientific return of the instrument. In this work, we will describe the various phases of construction, testing, and qualification prior to the launch and the in-flight operations of the instrument on board the ISS.
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| 15. |
- Melin, Beatrice S., et al.
(author)
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Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors
- 2017
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 789-794
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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| 16. |
- Ostrom, Quinn T., et al.
(author)
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Evaluating glioma risk associated with extent of European admixture in African-Americans and Latinos
- 2018
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In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 78:13
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Journal article (other academic/artistic)abstract
- Glioma incidence is highest in non-Hispanic Whites, where it occurs ~2x as frequently compared with other race/ethnicity groups. Glioma GWAS to date have included European ancestry populations only, and it is unknown whether variants identified by these analyses are associated with glioma in non- European ancestry populations. African Americans and Hispanics are admixed populations with varying proportions of European ancestry. While global ancestry may be similar within admixed groups, the proportion of European ancestry at each allele can vary across the genome. As glioma is more common in European ancestry populations, the presence of increased local European ancestry in these admixed populations could be used to identify glioma risk loci. Here we assessed whether excess European ancestry at established risk loci (Melin et al, Nature Genetics, 2017) was associated with glioma risk in non-European ancestry populations. Global ancestry was estimated using fastStructure, and local ancestry was estimated using RFMix. Both methods used 1,000 genomes project reference populations (African: YRI; European: CEU; East Asian: CHB/JPT; and Native American: CLM/PEL/MXL). We evaluated differences in local European ancestry between cases and controls using logistic regression conditioned on global European ancestry within 500kb of 25 previously identified risk variants among individuals with ≥50% African ancestry, and ≥30% Native American ancestry for all gliomas, and for grade IV glioblastoma (GBM) and grade II-III non-GBM. There were 347 individuals (184 cases and 163 controls) with ≥50% global African ancestry, and 277 individuals (153 cases and 124 controls) with ≥30% global American ancestry. There was no significant difference in proportion of global European ancestry between cases and controls with ≥50% global African ancestry (cases: 18.2%, controls: 17.7%, p=0.6834), and no significant difference in proportion of global European ancestry between cases and controls with ≥30% global American ancestry (cases: 51.1%, controls: 49.0%, p=0.2123). Among individuals with >50% African ancestry, we observed a nominally significant association between all glioma and increased local European ancestry at 7p11.2 (EGFR, pmin=0.0070) and between GBM and increased local European ancestry at 22q13.1 (CSNK1E, pmin=0.0098), both near SNPs previously associated with glioblastoma in majority European-ancestry populations. The dataset used for this analysis represents the largest collection of genotyped non-European glioma cases. These results suggest that glioma risk in African Americans may be associated with an increased local European ancestry variants at glioma risk loci previously identified in majority European ancestry populations (7p11.2 and 22q13.1).
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| 17. |
- Ostrom, Quinn T., et al.
(author)
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Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics
- 2020
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:3, s. 739-748
-
Journal article (peer-reviewed)abstract
- Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with >= 40% AA (AFR(>= 0.4)), and >= 15% NAA (AMR(>= 0.15)), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 x 10(-4); 11p11.12, p = 7.0 x 10-4) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR(>= 0.4). In addition, we identified a peak at rs1620291 (p = 4.36 x 10(-6)) in 7q21.3. Among AMR(>= 0.15), we found an association between increased EA in one region (12q24.21, p = 8.38 x 10(-4)), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 x 10(-4)). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies. What's new? Glioma is rare in non-White populations, and most glioma genome-wide association studies have included only primarily European ancestry populations. Here, the authors assess whether variation in European ancestry is associated with glioma risk in populations with a combination of European, African and Native American ancestry. Based on African American and Hispanic cases from two large glioma case-control studies, this analysis shows that increased European ancestry in admixed populations may be associated with increased glioma risk. The associations between glioma and two chromosomal regions previously identified in European ancestry populations, and four novel regions, may guide future studies.
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| 18. |
- Ackermann, Markus, et al.
(author)
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High-energy and ultra-high-energy neutrinos : A Snowmass white paper
- 2022
-
In: Journal of High Energy Astrophysics. - : Elsevier. - 2214-4048 .- 2214-4056. ; 36, s. 55-110
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Journal article (peer-reviewed)abstract
- Astrophysical neutrinos are excellent probes of astroparticle physics and high-energy physics. With energies far beyond solar, supernovae, atmospheric, and accelerator neutrinos, high-energy and ultrahigh-energy neutrinos probe fundamental physics from the TeV scale to the EeV scale and beyond. They are sensitive to physics both within and beyond the Standard Model through their production mechanisms and in their propagation over cosmological distances. They carry unique information about their extreme non-thermal sources by giving insight into regions that are opaque to electromagnetic radiation. This white paper describes the opportunities astrophysical neutrino observations offer for astrophysics and high-energy physics, today and in coming years.
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| 19. |
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| 20. |
- Casolino, M., et al.
(author)
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Observation of night-time emissions of the Earth in the near UV range from the International Space Station with the Mini-EUSO detector
- 2023
-
In: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257 .- 1879-0704. ; 284, s. 113336-
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Journal article (peer-reviewed)abstract
- Mini-EUSO (Multiwavelength Imaging New Instrument for the Extreme Universe Space Observatory) is a telescope observing the Earth from the International Space Station since 2019. The instrument employs a Fresnel-lens optical system and a focal surface composed of 36 Multi-Anode Photomultiplier tubes, 64 channels each, for a total of 2304 channels with single photon counting sensitivity. Mini-EUSO also contains two ancillary cameras to complement measurements in the near infrared and visible ranges. The scientific objectives of the mission range from the search for Extensive Air Showers (EAS) generated by Ultra-High Energy Cosmic Rays (UHECRs) with energies above 10(21) eV, the search for nuclearites and Strange Quark Matter (SQM), up to the study of atmospheric phenomena such as Transient Luminous Events (TLEs), meteors and meteoroids. Mini-EUSO can map the night-time Earth in the near UV range (predominantly between 290-430 nm) with a spatial resolution of about 6.3 km (full field of view equal to 44 degrees) and a maximum temporal resolution of 2.5 mu s, observing our planet through a nadir-facing UV-transparent window in the Russian Zvezda module. The detector saves triggered transient phenomena with a sampling rate of 2.5 mu s and 320 mu s, as well as continuous acquisition at 40.96 ms scale. In this paper we discuss the detector response and the flat-fielding and calibration procedures. Using the 40.96 ms data, we present similar or equal to 6.3 km resolution night-time Earth maps in the UV band, and report on various emissions of anthropogenic and natural origin. We measure ionospheric airglow emissions of dark moonless nights over the sea and ground, studying the effect of clouds, moonlight, and artificial (towns, boats) lights. In addition to paving the way forward for the study of long-term variations of light of natural and artificial origin, we also estimate the observation live-time of future UHECR detectors.
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