dmm049790.pdf (892.09 kB)
Translating non-coding genetic associations into a better understanding of immune-mediated disease.
journal contributionposted on 2023-03-13, 11:09 authored by Christina T Stankey, James C Lee
Genome-wide association studies have identified hundreds of genetic loci that are associated with immune-mediated diseases. Most disease-associated variants are non-coding, and a large proportion of these variants lie within enhancers. As a result, there is a pressing need to understand how common genetic variation might affect enhancer function and thereby contribute to immune-mediated (and other) diseases. In this Review, we first describe statistical and experimental methods to identify causal genetic variants that modulate gene expression, including statistical fine-mapping and massively parallel reporter assays. We then discuss approaches to characterise the mechanisms by which these variants modulate immune function, such as clustered regularly interspaced short palindromic repeats (CRISPR)-based screens. We highlight examples of studies that, by elucidating the effects of disease variants within enhancers, have provided important insights into immune function and uncovered key pathways of disease.
Crick (Grant ID: CC2219, Grant title: Lee CC2219)