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Journal Article

Understanding Alzheimer Disease at the interface between genetics and transcriptomics

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Verheijen, J., & Sleegers, K. (2018). Understanding Alzheimer Disease at the interface between genetics and transcriptomics. Trends in Genetics, 34(6), 434-447. doi:10.1016/j.tig.2018.02.007.

Cite as: https://hdl.handle.net/21.11116/0000-0006-DD42-7
Over 25 genes are known to affect the risk of developing Alzheimer disease (AD), the most common neurodegenerative dementia. However, mechanistic insights and improved disease management remains limited, due to difficulties in determining the functional consequences of genetic associations. Transcriptomics is increasingly being used to corroborate or enhance interpretation of genetic discoveries. These approaches, which include second and third generation sequencing, single-cell sequencing, and bioinformatics, reveal allele-specific events connecting AD risk genes to expression profiles, and provide converging evidence of pathophysiological pathways underlying AD. Simultaneously, they highlight brain region- and cell-type-specific expression patterns, and alternative splicing events that affect the straightforward relation between a genetic variant and AD, re-emphasizing the need for an integrated approach of genetics and transcriptomics in understanding AD. © 2018 The Authors