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Abstract
Aim: This article aims to evaluate the performance of a recent method to estimate heritability of continuous and binary traits, specifically in the context of pharmacogenetic studies. Materials & methods: The approach to be evaluated was designed to estimate heritability in large-scale disease studies. Extensive simulation studies designed to emulate common scenarios seen in pharmacogenetic studies were performed to elucidate the potential utility of this approach outside of disease genetics. The simulations cover continuous and binary traits with small-to-moderate heritability values across a variety of samples sizes in genome-wide, as well as candidate gene, settings. Results: On a genome-wide scale, a combination of relatively large sample sizes (i.e., n ≥ 1000) and at least moderate underlying heritability (i.e., ≥0.25) are needed in order to attain reasonable statistical power. However, in candidate gene studies, reasonable power can be attained across a more broad range of scenarios. Conclusion: Our simulation studies show that the proposed approach has clear utility in the context of pharmacogenetic studies, especially in candidate gene settings, and provides novel supplementary information that can be used to inform decision-making in the pharmaceutical industry.
Original submitted 1 November 2012; Revision submitted 24 January 2013
Financial & competing interests disclosure
This study results from the employment of all authors by BioStat Solutions, Inc. (BSSI) and Eli Lilly and Co. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.