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Controlling false discoveries in candidate gene studies

Molecular Psychiatry volume 10, pages 230–231 (2005)Cite this article

Adjustments for multiple testing are rare in situations where a modest number of markers are typed, such as candidate genes studies. Based on a simulation study, we argue that this can result in a considerable risk of false discoveries, but that a simple and efficient method can be used to counteract this.

We noted that in studies where relatively few tests are performed, such as candidate genes studies, adjustments for multiple testing are rare. The reasons are not clear. As few tests are performed compared to linkage (disequilibrium) scans, the risk of false discoveries is perhaps perceived to be small. Geneticists could also be reluctant to correct for multiple testing because this may result in a low power to detect real effects. Furthermore, markers in candidate gene studies are often in linkage disequilibrium and analyzed in multiple ways (eg as single markers or part of haplotypes). Procedures to control false discoveries are sometimes considered inappropriate for such correlated tests.1 The pattern that emerges from the analyses may sometimes seem meaningful. For instance, finding a more significant haplotype could be viewed as a confirmation that a significant single marker was not a false discovery. Researchers might feel that methods for controlling false discoveries are too conservative since they cannot take this kind of information into account. The same might be true for other forms of ‘circumstantial evidence,’ such as a significant result for markers that are functional or show similar genotype–phenotype associations in other species.

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Acknowledgements

This work was supported in part by grants from the NIMH (MH065320) and NARSAD. The coalescent simulations were performed using code from the program MS (http://home.uchicago.edu/~rhudson1/source/mksamples.html), and I thank Kui Zhang for making his source code available to select the haplotype tag SNPs.

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  1. Virginia Institute for Psychiatric and Behavioral Genetics, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA, USA

    E J C G van den Oord

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  1. E J C G van den Oord
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Correspondence to E J C G van den Oord.

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van den Oord, E. Controlling false discoveries in candidate gene studies. Mol Psychiatry 10, 230–231 (2005). https://doi.org/10.1038/sj.mp.4001581

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