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- 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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- 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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- Cordon, O, et al.
(författare)
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Ten years of genetic fuzzy systems : current framework and new trends
- 2004
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Ingår i: Fuzzy sets and systems (Print). - 0165-0114 .- 1872-6801. ; 141:1, s. 5-31
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Forskningsöversikt (refereegranskat)abstract
- Fuzzy systems have demonstrated their ability to solve different kinds of problems in various application domains. Currently, there is an increasing interest to augment fuzzy systems with learning and adaptation capabilities. Two of the most successful approaches to hybridise fuzzy systems with learning and adaptation methods have been made in the realm of soft computing. Neural fuzzy systems and genetic fuzzy systems hybridise the approximate reasoning method of fuzzy systems with the learning capabilities of neural networks and evolutionary algorithms. The objective of this paper is to provide an account of genetic fuzzy systems, with special attention to genetic fuzzy rule-based systems. After a brief introduction to models and applications of genetic fuzzy systems, the field is overviewed, new trends are identified, a critical evaluation of genetic fuzzy systems for fuzzy knowledge extraction is elaborated, and open questions that remain to be addressed in the future are raised. The paper also includes some of the key references required to quickly access implementation details of genetic fuzzy systems.
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