| 1. |
- 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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| 2. |
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| 3. |
- 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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| 4. |
- Householder, John Ethan, et al.
(författare)
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One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
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Tidskriftsartikel (refereegranskat)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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| 5. |
- Luize, Bruno Garcia, et al.
(författare)
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Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
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Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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| 6. |
- Reinke, Beth A, et al.
(författare)
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Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
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Tidskriftsartikel (refereegranskat)abstract
- Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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| 7. |
- ter Steege, Hans, et al.
(författare)
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Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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| 8. |
- Watts, Eleanor L., et al.
(författare)
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Observational and genetic associations between cardiorespiratory fitness and cancer : a UK Biobank and international consortia study
- 2024
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130, s. 114-124
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association of fitness with cancer risk is not clear.Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.
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| 9. |
- Brandão, Andreia, et al.
(författare)
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The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
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| 10. |
- Nutter, S., et al.
(författare)
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Changing the global obesity narrative to recognize and reduce weight stigma: A position statement from the World Obesity Federation
- 2023
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Ingår i: Obesity Reviews. - 1467-7881. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Weight stigma, defined as pervasive misconceptions and stereotypes associated with higher body weight, is both a social determinant of health and a human rights issue. It is imperative to consider how weight stigma may be impeding health promotion efforts on a global scale. The World Obesity Federation (WOF) convened a global working group of practitioners, researchers, policymakers, youth advocates, and individuals with lived experience of obesity to consider the ways that global obesity narratives may contribute to weight stigma. Specifically, the working group focused on how overall obesity narratives, food and physical activity narratives, and scientific and public-facing language may contribute to weight stigma. The impact of weight stigma across the lifespan was also considered. Taking a global perspective, nine recommendations resulted from this work for global health research and health promotion efforts that can help to reduce harmful obesity narratives, both inside and outside health contexts.
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