| 1. |
- 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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| 2. |
- 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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| 6. |
- Huynh-Le, MP, et al.
(författare)
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Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1236-
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Tidskriftsartikel (refereegranskat)abstract
- Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
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| 8. |
- Ranchhod, S. M., et al.
(författare)
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Potential neuroprotective strategies for perinatal infection and inflammation
- 2015
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 0736-5748 .- 1873-474X. ; 45, s. 44-54
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Tidskriftsartikel (refereegranskat)abstract
- Preterm born infants have high rates of brain injury, leading to motor and neurocognitive problems in later life. Infection and resulting inflammation of the fetus and newborn are highly associated with these disabilities. However, there are no established neuroprotective therapies. Microglial activation and expression of many cytokines play a key role in normal brain function and development, as well as being deleterious. Thus, treatment must achieve a delicate balance between possible beneficial and harmful effects. In this review, we discuss potential neuroprotective strategies targeting systemic infection or the resulting systemic and central inflammatory responses. We highlight the central importance of timing of treatment and the critical lack of studies of delayed treatment of infection/inflammation. (C) 2015 Elsevier Ltd. All rights reserved.
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| 9. |
- Hakman, Inger, et al.
(författare)
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A light and electron-microscope study of Picea glauca (White spruce) somatic embryos
- 1987
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Ingår i: Protoplasma. - 0033-183X .- 1615-6102. ; 140:2-3, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- Somatic embryos in embryogenic callus cultures derived fromimmature zygotic embryos of Picea glauca (White spruce) wereexamined by light and electron microscopy. Somatic embryos consistof an embryonic region of small densely cytoplasmic cells subtendedby a suspensor consisting of long highly vaeuolated cells. Mitoticfigures are frequent in the embryonic cells but are not observed in thesuspensor. Cell divisions in the embryonic region apparently producerows of cells which elongate to form the suspensor. The presence ofabundant polysomes, coated membranes and dictyosomes in thecytoplasm of embryonic and upper suspensor cells suggests rapidgrowth of the embryo. In contrast the basipetal suspensor cellsappear to be senescing. While only a few scattered microfilaments arepresent in the meristematic celIs, the upper suspensor cells containnumerous bundles of longitudinally oriented microfitaments. Thesebundles correspond to actin cables observed in light microscopepreparations stained with rhodamine labelled phalloidin and areoriented parallel to the direction of active streaming in these cells.
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| 10. |
- Hakman, Inger, et al.
(författare)
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An embryogenic cell-suspension culture of Picea glauca (White spruce)
- 1987
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Ingår i: Plant Cell Reports. - 0721-7714 .- 1432-203X. ; 6:1, s. 20-22
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Tidskriftsartikel (refereegranskat)abstract
- A cell suspension culture of Picea glauca (White spruce) which continuously produces somatic embryos has been established. Embryogenic callus derived from cultured zygotic embryos was used to initiate the culture. Numerous embryos at various early stages of development were recognized; they exhibited a meristematic embryonic region and suspensor consisting of elongate, vacuolated cells. The culture also contained clumps of meristematic cells and large irregular — shaped cells. The culture could be readily re-established on solid medium.
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