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- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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- Foster, Joshua W., et al.
(författare)
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Extraterrestrial Axion Search with the Breakthrough Listen Galactic Center Survey
- 2022
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 129:25
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Tidskriftsartikel (refereegranskat)abstract
- Axion dark matter (DM) may efficiently convert to photons in the magnetospheres of neutron stars (NSs), producing nearly monochromatic radio emission. This process is resonantly triggered when the plasma frequency induced by the underlying charge distribution approximately matches the axion mass. We search for evidence of this process using archival Green Bank Telescope data collected in a survey of the Galactic Center in the C band by the Breakthrough Listen project. While Breakthrough Listen aims to find signatures of extraterrestrial life in the radio band, we show that their high-frequency resolution spectral data of the Galactic Center region is ideal for searching for axion-photon transitions generated by the population of NSs in the inner pc of the Galaxy. We use data-driven models to capture the distributions and properties of NSs in the inner Galaxy and compute the expected radio flux from each NS using state-of-the-art ray tracing simulations. We find no evidence for axion DM and set leading constraints on the axion-photon coupling, excluding values down to the level ga gamma gamma similar to 10-11 GeV-1 for DM axions for masses between 15 and 35
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- Griep, Yannick, et al.
(författare)
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Voluntary Work and the Relationship With Unemployment, Health, and Well-Being : a Two-Year Follow-Up Study Contrasting a Materialistic and Psychosocial Pathway Perspective.
- 2015
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Ingår i: Journal of Occupational Health Psychology. - : American Psychological Association (APA). - 1076-8998 .- 1939-1307. ; 20:2, s. 190-204
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we contrast materialistic (i.e., income and economic inequality) and psychosocial (i.e., social circumstances) pathway perspectives on whether volunteering while being unemployed mitigates the well-documented negative effects of unemployment on health, health behaviors, and well-being. We test our hypotheses using data from the 2010 and 2012 waves of the Swedish Longitudinal Occupational Study of Health (SLOSH; n = 717). This is a nationally representative, longitudinal, cohort survey. We compared groups of individuals who were (a) unemployed and volunteering during both SLOSH waves (n = 58), (b) unemployed and not volunteering during both SLOSH waves (n = 194), (c) employed and volunteering during both SLOSH waves (n = 139), and (d) employed and not volunteering during both SLOSH waves (n = 326). Conducting a path analysis in Mplus, we examined the interaction effects between labor market status (i.e., employed or unemployed) and voluntary work (i.e., volunteering or not) when predicting changes in health, health behaviors, and psychological well-being. Our results indicate that volunteering during unemployment significantly decreased the likelihood to smoke, the amount of cigarettes smoked, the likelihood of consuming alcohol, and the likelihood of being diagnosed with hypertension. These results support a psychosocial pathway perspective. For all other indicators no such buffering interaction effect was obtained, thereby supporting a materialistic pathway perspective. Nevertheless, for some indicators, volunteering was found to be beneficial for both the unemployed and employed. Consequently, integrating both perspectives might offer a better explanation for the onset of ill-health and ill-being.
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- Kottyan, Leah C., et al.
(författare)
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The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
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Tidskriftsartikel (refereegranskat)abstract
- Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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- Thomas, Sinju, et al.
(författare)
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Effects of material properties of band-gap-graded Cu(In,Ga)Se-2 thin films on the onset of the quantum efficiency spectra of corresponding solar cells
- 2022
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Ingår i: Progress in Photovoltaics. - : John Wiley & Sons. - 1062-7995 .- 1099-159X. ; 30:10, s. 1238-1246
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Tidskriftsartikel (refereegranskat)abstract
- Polycrystalline Cu(In,Ga)Se-2 (CIGSe) thin-film solar cells exhibit gradual onset in their external quantum efficiency (EQE) spectra whose shape can be affected by various CIGSe material properties. Apart from influences on the charge-carrier collection, a broadening of the EQE onset leads to enhanced radiative losses in open-circuit voltage (V-oc). In the present work, Gaussian broadening of parameters describing the EQE onset of thin-film solar cells, represented by the standard deviation, sigma(total), was evaluated to study the impacts of the effective band-gap energy, the electron diffusion length, and the Ga/In gradient in the CIGSe absorber. It is shown that sigma(total) can be disentangled into contributions of these material properties, in addition to a residual component sigma(residual). Effectively, sigma(total) depends only on a contribution related to the Ga/In gradient as well as on sigma(residual). The present work highlights the connection of this compositional gradient, the microstructure in the polycrystalline CIGSe absorber, and the luminescence emission with the residual component sigma(residual). It is demonstrated that a flat band-gap with no compositional gradient in the bulk of the CIGSe absorber is essential to obtain the lowest sigma(total) values and thus result in lower recombination losses and gains in V-oc.
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7. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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