The need to shift pharmacogenetic research from candidate gene to genome-wide association studies

Abstract

The primary research approach in pharmacogenetics has been candidate gene association studies (CGAS), but pharmacogenomic genome-wide association studies (GWAS) are becoming more common. We are now at a critical juncture when the results of those two research approaches, CGAS and GWAS, can be compared in pharmacogenetics. We analyzed publicly available databases of pharmacogenetic CGAS and GWAS (i.e., the Pharmacogenomics Knowledgebase [PharmGKB®] and the NHGRI-EBI GWAS catalog)and the vast majority of variants (98%) and genes (94%) discovered in pharmacogenomic GWAS were novel (i.e., not previously studied CGAS). Therefore, pharmacogenetic researchers are not selecting the right candidate genes in the vast majority of CGAS, highlighting a need to shift pharmacogenetic research efforts from CGAS to GWAS.