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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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- Smalley, Alexander J., et al.
(författare)
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Soundscapes, music, and memories : Exploring the factors that influence emotional responses to virtual nature content
- 2023
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Ingår i: Journal of Environmental Psychology. - : Elsevier BV. - 0272-4944 .- 1522-9610. ; 89
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Tidskriftsartikel (refereegranskat)abstract
- From walking through a park to sitting on a beach, much is known about the therapeutic potential of direct contact with natural environments. Yet routinely in the UK, millions of people encounter nature in a completely different way: through their television screens. Despite the ubiquity of natural history programming, little is understood about its impact on the restorative and affective experiences of audiences. Nowhere is this truer than in the bold orchestral scores that accompany almost all nature documentaries. Whilst considerable evidence suggests that separately, both nature and music can provide a range of psychological benefits, how their pairing might affect the wellbeing potential of virtual nature encounters remains largely unknown. Similarly, scant research has considered how viewers' own experiences, recalled through memories, might influence outcomes. To explore these areas, we formed a transdisciplinary broadcast initiative, called BBC Soundscapes for Wellbeing. Part of this project involved a randomized and controlled experiment that presented participants (n = 7636) with a dynamic nature scene accompanied by one of four acoustic tracks. Results demonstrated that whilst adding music to this scene led to increased feelings of excitement, it led to no other restorative or affective benefits when compared to silence. In contrast, the addition of natural sounds was associated with greater feelings of restorative potential, calmness, and excitement. Natural sounds also drove significant increases in the complex emotions of awe and nostalgia. Crucially, results showed the substantial moderating effects of participant memories. Those with positive memories stimulated by the experience reported significantly greater effects across all conditions and dependent variables. We find that although the acoustic design of virtual nature encounters can affect a range of emotional responses, the memories triggered by these experiences may be far more important for predicting viewer outcomes.
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