9 research outputs found
New insights into the genetic etiology of Alzheimer's disease and related dementias
- Author
- Aaltonen L.
- Aaltonen V.
- Aarsland Dag
- Aavikko M.
- Abalos M.S.
- Abdelnour Carla
- Abner E.
- Abraham R.
- Adams H.
- Adams P.M.
- Adarmes-GĂłmez A.
- Adarmes-GĂłmez A.D.
- Aguilera N.
- Aguilera N.
- Aguirre A.
- Ahmad S.
- Akinyemi R.O.
- Al-Chalabi A.
- AlarcĂłn-MartĂn Emilio
- Albert M.S.
- Albin R.L.
- Alcolea Daniel
- Alegret Montserrat
- Ali M.
- Allen M.
- Allende I.R.
- Alonso M.D.
- Alonso M.D.
- Alvarez I.
- Alvarez L.
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- Amouyel Philippe
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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 Δ4 allele
Biotransformation of trichothecene mycotoxins during fermentation with lager yeast
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- Field of study
Biotransformation of trichothecene mycotoxins during fermentation with lager yeast
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- Field of study
Impact of External Nasal Strips on Nasal Geometry and Intranasal Air-conditioning
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- Field of study
Riduzione di dose radiante mediante utilizzo della TC a fascio conico nei pazienti ipoacusici
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- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Common variants in Alzheimerâs disease and risk stratification by polygenic risk scores
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- 01/01/2021
- Field of study
Genetic discoveries of Alzheimerâs 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 nâ=â409,435 and validation size nâ=â58,190). Here, we add six variants associated with Alzheimerâs 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 Alzheimerâs disease patients in APOE É4 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 Alzheimerâs disease
Common variants in Alzheimerâs disease and risk stratification by polygenic risk scores
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2021
- Field of study
Genetic discoveries of Alzheimerâs 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 Alzheimerâs 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 Alzheimerâs disease patients in APOE É4 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 Alzheimerâs disease. © 2021, The Author(s)
Common variants in Alzheimerâs disease and risk stratification by polygenic risk scores
- Publication venue
- Publication date
- 01/01/2021
- Field of study
Genetic discoveries of Alzheimerâs 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 Alzheimerâs 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 Alzheimerâs disease patients in APOE É4 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 Alzheimerâs disease. © 2021, The Author(s)
New insights into the genetic etiology of Alzheimerâs disease and related dementias
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimerâs 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/âproxyâ 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 Δ4 allele. © 2022, The Author(s)