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| 14. |
- Barnes, DR, et al.
(författare)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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- Bigelow, NH, et al.
(författare)
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Climate change and Arctic ecosystems: 1. Vegetation changes north of 55 degrees N between the last glacial maximum, mid-Holocene, and present
- 2003
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Ingår i: Journal of Geophysical Research. - 2156-2202. ; 108:D19
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Forskningsöversikt (refereegranskat)abstract
- [1] A unified scheme to assign pollen samples to vegetation types was used to reconstruct vegetation patterns north of 55degreesN at the last glacial maximum (LGM) and mid-Holocene (6000 years B. P.). The pollen data set assembled for this purpose represents a comprehensive compilation based on the work of many projects and research groups. Five tundra types (cushion forb tundra, graminoid and forb tundra, prostrate dwarf-shrub tundra, erect dwarf-shrub tundra, and low- and high-shrub tundra) were distinguished and mapped on the basis of modern pollen surface samples. The tundra-forest boundary and the distributions of boreal and temperate forest types today were realistically reconstructed. During the mid-Holocene the tundra-forest boundary was north of its present position in some regions, but the pattern of this shift was strongly asymmetrical around the pole, with the largest northward shift in central Siberia (similar to200 km), little change in Beringia, and a southward shift in Keewatin and Labrador (similar to200 km). Low- and high-shrub tundra extended farther north than today. At the LGM, forests were absent from high latitudes. Graminoid and forb tundra abutted on temperate steppe in northwestern Eurasia while prostrate dwarf-shrub, erect dwarf-shrub, and graminoid and forb tundra formed a mosaic in Beringia. Graminoid and forb tundra is restricted today and does not form a large continuous biome, but the pollen data show that it was far more extensive at the LGM, while low- and high-shrub tundra were greatly reduced, illustrating the potential for climate change to dramatically alter the relative areas occupied by different vegetation types.
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- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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