Genomics-driven drug discovery based on disease-susceptibility genes

Abstract

Genome-wide association studies have identified numerous disease-susceptibility genes. As knowledge of gene-disease associations accumulates, it is becoming increasingly important to translate this knowledge into clinical practice. This challenge involves finding effective drug targets and estimating their potential side effects, which often results in failure of promising clinical trials. Here, we review recent advances and future perspectives in genetics-led drug discovery, with a focus on drug repurposing, Mendelian randomization, and the use of multifaceted omics data.

Fig. 1

Schematic comparison between the randomized controlled trial and Mendelian randomization. Two schematic diagrams are shown for Mendelian randomization separately for the effect direction of the non-reference allele, i.e. protective or causal (risk allele). For simplicity, a single genomic locus is depicted in the diagrams of Mendelian randomization. Note that multiple loci are considered for statistical evaluation in practical settings. In RCT, random assignment of a treatment minimizes the effects of confounders. In MR, random segregation of alleles during gamete formation plays a similar role