Using High-Throughput Animal or Cell-Based Models to Functionally Characterize GWAS Signals

• Published in: Current genetic medicine reports Vol. 6; no. 3; pp. 107 - 115
• Main Authors: Dourlen, Pierre, Chapuis, Julien, Lambert, Jean-Charles
• Format: Journal Article
• Language: English
• Published: New York Springer US 2018; Springer Nature B.V; Springer
• Subjects: Alzheimer's disease; Animal models; Cell culture; Genome-wide association studies; Genomes; High-throughput screening; Internal Medicine; Life Sciences; Medicine; Medicine & Public Health; Neurogenetics and Psychiatric Genetics (C Cruchaga; Neurogenetics and Psychiatric Genetics (C Cruchaga, Section Editor); Section Editor; Single-nucleotide polymorphism; Topical Collection on Neurogenetics and Psychiatric Genetics; HCS; GWAS; Alzheimer; HTS; Screen; Drosophila
• ISSN: 2167-4876; 2167-4876
• DOI: 10.1007/s40142-018-0141-1

Purpose of Review
The advent of genome-wide association studies (GWASs) constituted a breakthrough in our understanding of the genetic architecture of multifactorial diseases. For Alzheimer’s disease (AD), more than 20 risk loci have been identified. However, we are now facing three new challenges: (i) identifying the functional SNP or SNPs in each locus, (ii) identifying the causal gene(s) in each locus, and (iii) understanding these genes’ contribution to pathogenesis.
Recent Findings
To address these issues and thus functionally characterize GWAS signals, a number of high-throughput strategies have been implemented in cell-based and whole-animal models. Here, we review high-throughput screening, high-content screening, and the use of the
Drosophila
model (primarily with reference to AD).
Summary
We describe how these strategies have been successfully used to functionally characterize the genes in GWAS-defined risk loci. In the future, these strategies should help to translate GWAS data into knowledge and treatments.