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

The Pharmacogenomics Journal volume 16, pages 388–392 (2016)Cite this article

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Abstract

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.

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Acknowledgements

JCM was supported by a Clinical Therapeutics training grant to the University of Chicago (T32GM007019). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL, USA

    J C Maranville & N J Cox

  2. Department of Medicine, The University of Chicago, Chicago, IL, USA

    J C Maranville & N J Cox

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  1. J C Maranville
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  2. N J Cox
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Correspondence to J C Maranville.

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Maranville, J., Cox, N. Pharmacogenomic variants have larger effect sizes than genetic variants associated with other dichotomous complex traits. Pharmacogenomics J 16, 388–392 (2016). https://doi.org/10.1038/tpj.2015.47

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