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- W2897736066 abstract "It is well known that drug therapies underpinned by genetic evidence of disease association, are more likely to progress through trials to the clinic. Moreover, the level of evidence required to attain genome-wide significance in genetic studies is stringent. It is therefore surprising that the association between APOE and Alzheimer's disease (AD) originally published by the Roses group over two decades ago, showing compelling evidence of association and an effect size larger than most common genetic associations with any phenotype, is so under researched. It is true that APOE has several potential roles and was difficult to model in the early days. It may also be argued that it is only lately that we are beginning to capture the full genetic complexity of Alzheimer's disease to provide a context in which APOE could be understood. My collaborative work in this field has shown strong patterns of relationship between putative disease components, such as immunity, endocytosis and cholesterol transport, amongst others. We have now identified over 27 genetic loci known to influence AD at a genome-wide level of significance and algorithms based upon thousands of genetic variants are now able to predict AD with around 80% accuracy, which rises to over 90% at the polygenic extremes. Building on these findings and taking advantage of advances in stem cell manipulation, both isogenic and from genetically profiled individuals, complex animal modelling, incorporating chimeric and conditional methodologies and exploiting the precision of single cell omic analyses with big data approaches, we are far better placed now to identify how APOE and other associated risk variants influence the full complexity of Alzheimer's disease." @default.
- W2897736066 created "2018-10-26" @default.
- W2897736066 creator A5040824243 @default.
- W2897736066 date "2018-07-01" @default.
- W2897736066 modified "2023-10-16" @default.
- W2897736066 title "F2‐03‐02: GENETICS IS MORE IMPORTANT THAN EVER IN DIRECTING OUR UNDERSTANDING OF ALZHEIMER'S DISEASE" @default.
- W2897736066 doi "https://doi.org/10.1016/j.jalz.2018.06.2620" @default.
- W2897736066 hasPublicationYear "2018" @default.
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