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IJE Advance Access originally published online on October 30, 2007
International Journal of Epidemiology 2007 36(6):1363-1369; doi:10.1093/ije/dym215
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Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2007; all rights reserved.

Investigating gene–environment interaction in complex diseases: increasing power by selective sampling for environmental exposure

M P M Boks1,*, M Schipper2, C D Schubart1, I E Sommer1, R S Kahn1 and R A Ophoff3,4

1The Rudolf Magnus Institute of Neuroscience, Department of Psychiatry University Medical Centre Utrecht, Utrecht, The Netherlands.
2Centre for Biostatistics, University of Utrecht, Utrecht, The Netherlands.
3The Rudolf Magnus Institute of Neuroscience, Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
4The Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA.

*Corresponding author. Rudolf Magnus Institute of Neuroscience, Department of Psychiatry B01.206, University Medical Centre Utrecht, PO box 85500, 3508 GA Utrecht, The Netherlands. E-mail: mboks{at}umcutrecht.nl


  Abstract

Background The often limited influence of disease associated alleles on the vulnerability to complex diseases has lead to increased interest in environmental interaction with genotype. However, gene environmental interactions (GEIs) are not easily studied, since high numbers of subjects are required to detect GEI.

Methods and results This study provides a potential useful method to increase the power of such studies through selective sampling for environmental exposure. We show that selecting the top and bottom 10% regarding environmental exposure can lead to a 70% reduction in the required number of subjects for genotyping.

Conclusion This study demonstrates the potential usefulness of selective sampling in the study of the interplay between genes and environment. The reduction of required subjects can be particularly advantageous in studies where genotyping is extensive, such as in whole genome screens or in studies where phenotyping is expensive.

Keywords Genotype, gene–environment interaction, environmental exposure, sample size, quantitative trait

Accepted 26 September 2007


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