Genome-wide association studies have identified thousands of variants with putative roles in different diseases and complex traits. However, going from statistical associations to true insight into mechanisms of disease or biology remains an incredible challenge for the field. As most genome-wide significant variants are found in non-coding regions, linking these SNPs to genes or pathways is not trivial. Additionally, genetic architecture and linkage disequilibrium make it difficult to discern truly causal from merely correlative associations.
Recent advances in sequencing technologies have allowed for the development of genomics-based strategies for assaying GWAS SNPs for potential functional relevance. High-throughput approaches that are capable of testing thousands of variants will help to prioritize functional SNPs and further our understanding about the genes and the regulatory pathways that are relevant for specific phenotypes. Powerful combinations of high-throughput experimental assays, single-cell approaches and computational analyses are accelerating the ability to link variants to function, and by extension, link genotype to phenotype.
Department of Bioengineering and Theraputic Sciences Institute for Human Genetics
University of California San Francisco
Sanger Institute and Experimental Science Director at Open Targets