| 21. |
- Brasky, Theodore M., et al.
(författare)
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Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium : An individual-participant meta-analysis
- 2023
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Ingår i: Gynecologic Oncology. - : Elsevier. - 0090-8258 .- 1095-6859. ; 169, s. 137-146
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Tidskriftsartikel (refereegranskat)abstract
- Background. Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial can-cer risk; particularly among certain subgroups characterized by body mass and tumor pathology.Materials and methods. Data from 12 prospective cohort studies participating in the Epidemiology of Endome-trial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid in-takes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study -specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk.Results. Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were as-sociated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not dif-fer by cancer grade.Conclusion. Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly over-weight/obese women.(c) 2022 Elsevier Inc. All rights reserved.
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| 22. |
- Gaudet, Mia M., et al.
(författare)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 23. |
- Gouliermis, Dimitrios A., et al.
(författare)
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Hierarchical star formation across the grand-design spiral NGC 1566
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 468:1, s. 509-530
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Tidskriftsartikel (refereegranskat)abstract
- We investigate how star formation is spatially organized in the grand-design spiral NGC 1566 from deep Hubble Space Telescope photometry with the Legacy ExtraGalactic UV Survey. Our contour-based clustering analysis reveals 890 distinct stellar conglomerations at various levels of significance. These star- forming complexes are organized in a hierarchical fashion with the larger congregations consisting of smaller structures, which themselves fragment into even smaller and more compact stellar groupings. Their size distribution, covering a wide range in length-scales, shows a power law as expected from scale-free processes. We explain this shape with a simple 'fragmentation and enrichment' model. The hierarchical morphology of the complexes is confirmed by their mass-size relation that can be represented by a power law with a fractional exponent, analogous to that determined for fractal molecular clouds. The surface stellar density distribution of the complexes shows a lognormal shape similar to that for supersonic non-gravitating turbulent gas. Between 50 and 65 per cent of the recently formed stars, as well as about 90 per cent of the young star clusters, are found inside the stellar complexes, located along the spiral arms. We find an age difference between young stars inside the complexes and those in their direct vicinity in the arms of at least 10 Myr. This time-scale may relate to the minimum time for stellar evaporation, although we cannot exclude the in situ formation of stars. As expected, star formation preferentially occurs in spiral arms. Our findings reveal turbulent-driven hierarchical star formation along the arms of a grand-design galaxy.
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| 24. |
- Jung, Dooseok Escher, et al.
(författare)
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Universal Upper End of the Stellar Initial Mass Function in the Young and Compact LEGUS Clusters
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 954:2
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the variation in the upper end of the stellar initial mass function (uIMF) in 375 young and compact star clusters in five nearby galaxies within ∼5 Mpc. All the young stellar clusters (YSCs) in the sample have ages ≲ 4 Myr and masses above 500 M⊙, according to standard stellar models. The YSC catalogs were produced from Hubble Space Telescope images obtained as part of the Legacy ExtraGalactic UV Survey (LEGUS) Hubble treasury program. They are used here to test whether the uIMF is universal or changes as a function of the cluster's stellar mass. We perform this test by measuring the Hα luminosity of the star clusters as a proxy for their ionizing photon rate, and charting its trend as a function of cluster mass. Large cluster numbers allow us to mitigate the stochastic sampling of the uIMF. The advantage of our approach relative to previous similar attempts is the use of cluster catalogs that have been selected independently of the presence of Hα emission, thus removing a potential sample bias. We find that the uIMF, as traced by the Hα emission, shows no dependence on cluster mass, suggesting that the maximum stellar mass that can be produced in star clusters is universal, in agreement with previous findings.
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| 25. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 26. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 27. |
- Gouliermis, Dimitrios A., et al.
(författare)
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Hierarchical star formation across the ring galaxy NGC 6503
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 452:4, s. 3508-3528
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed clustering analysis of the young stellar population across the star-forming ring galaxy NGC 6503, based on the deep Hubble Space Telescope photometry obtained with the Legacy ExtraGalactic UV Survey. We apply a contour-based map analysis technique and identify in the stellar surface density map 244 distinct star-forming structures at various levels of significance. These stellar complexes are found to be organized in a hierarchical fashion with 95 per cent being members of three dominant super-structures located along the star-forming ring. The size distribution of the identified structures and the correlation between their radii and numbers of stellar members show power-law behaviours, as expected from scale-free processes. The self-similar distribution of young stars is further quantified from their autocorrelation function, with a fractal dimension of similar to 1.7 for length-scales between similar to 20 pc and 2.5 kpc. The young stellar radial distribution sets the extent of the star-forming ring at radial distances between 1 and 2.5 kpc. About 60 per cent of the young stars belong to the detected stellar structures, while the remaining stars are distributed among the complexes, still inside the ring of the galaxy. The analysis of the time-dependent clustering of young populations shows a significant change from a more clustered to a more distributed behaviour in a time-scale of similar to 60 Myr. The observed hierarchy in stellar clustering is consistent with star formation being regulated by turbulence across the ring. The rotational velocity difference between the edges of the ring suggests shear as the driving mechanism for this process. Our findings reveal the interesting case of an inner ring forming stars in a hierarchical fashion.
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| 28. |
- Szatmari, Peter, et al.
(författare)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 29. |
- 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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