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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 3. |
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| 4. |
- 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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| 5. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 8. |
- Akrami, Y., et al.
(författare)
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Planck intermediate results LII. Planet flux densities
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 607
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of flux density are described for five planets, Mars, Jupiter, Saturn, Uranus, and Neptune, across the six Planck High Frequency Instrument frequency bands (100-857 GHz) and these are then compared with models and existing data. In our analysis, we have also included estimates of the brightness of Jupiter and Saturn at the three frequencies of the Planck Low Frequency Instrument (30, 44, and 70 GHz). The results provide constraints on the intrinsic brightness and the brightness time-variability of these planets. The majority of the planet flux density estimates are limited by systematic errors, but still yield better than 1% measurements in many cases. Applying data from Planck HFI, the Wilkinson Microwave Anisotropy Probe (WMAP), and the Atacama Cosmology Telescope (ACT) to a model that incorporates contributions from Saturn's rings to the planet's total flux density suggests a best fit value for the spectral index of Saturn's ring system of beta(ring) = 2 : 30 +/- 0 : 03 over the 30-1000 GHz frequency range. Estimates of the polarization amplitude of the planets have also been made in the four bands that have polarization-sensitive detectors (100-353 GHz); this analysis provides a 95% confidence level upper limit on Mars's polarization of 1.8, 1.7, 1.2, and 1.7% at 100, 143, 217, and 353 GHz, respectively. The average ratio between the Planck-HFI measurements and the adopted model predictions for all five planets (excluding Jupiter observations for 353 GHz) is 1.004, 1.002, 1.021, and 1.033 for 100, 143, 217, and 353 GHz, respectively. Model predictions for planet thermodynamic temperatures are therefore consistent with the absolute calibration of Planck-HFI detectors at about the three-percent level. We compare our measurements with published results from recent cosmic microwave background experiments. In particular, we observe that the flux densities measured by Planck HFI and WMAP agree to within 2%. These results allow experiments operating in the mm-wavelength range to cross-calibrate against Planck and improve models of radiative transport used in planetary science.
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| 10. |
- Sikdar, S, et al.
(författare)
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Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking
- 2019
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 11:13, s. 1487-1500
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.
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