Pharmacogenomic variants have larger effect sizes than genetic variants associated with other dichotomous complex traits.

Maranville JC, Cox NJ
Pharmacogenomics J. 2016 16 (4): 388-92

PMID: 26149738 · PMCID: PMC4704992 · DOI:10.1038/tpj.2015.47

It has been suggested that pharmacogenomic phenotypes are influenced by genetic variants with larger effect sizes than other phenotypes, such as complex disease risk. This is presumed to reflect the fact that relevant environmental factors (drug exposure) are appropriately measured and taken into account. To test this hypothesis, we performed a systematic comparison of effect sizes between pharmacogenomic and non-pharmacogenomic phenotypes across all genome-wide association studies (GWAS) reported in the NHGRI GWAS catalog. We found significantly larger effect sizes for studies focused on pharmacogenomic phenotypes, as compared with complex disease risk, morphological phenotypes and endophenotypes. We found no significant differences in effect sizes between pharmacogenomic studies focused on adverse events versus those focused on drug efficacy. Furthermore, we found that this pattern persists among sample size-matched studies, suggesting that this pattern does not reflect overestimation of effect sizes due to smaller sample sizes in pharmacogenomic studies.The Pharmacogenomics Journal advance online publication, 7 July 2015; doi:10.1038/tpj.2015.47.

MeSH Terms (12)

Databases, Genetic Drug-Related Side Effects and Adverse Reactions Endophenotypes Genetic Linkage Genetic Predisposition to Disease Genome-Wide Association Study Genotype Heredity Humans Pharmacogenomic Variants Phenotype Quantitative Trait, Heritable

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