On the use of allelic transmission rates for assessing gene-by-environment interaction in case-parent trios

Annals of Human Genetics
Ji-Hyung ShinJinko Graham

Abstract

Allelic transmission rates from parents to cases are frequently stratified by an environmental risk factor E and compared, with heterogeneity interpreted as gene-environment interaction or GxE. Though generally invalid, such analyses continue to appear. We revisit why heterogeneity is not equivalent to GxE in a range of settings not considered previously. The objective is a fuller understanding of the bias in transmission rates and what is driving it. Extending previously published findings, we derive parental mating-type probabilities in cases and use them to obtain transmission rates, which we then compare to GxE. Through simulation, we investigate the practical implications of the bias for a transmission-based test of GxE. We find that general population characteristics distort the picture of GxE obtained from transmission rates: the stratum-specific mating-type probabilities under G - E dependence and the allele frequency under independence. Furthermore, the transmission-based test has inflated error rates relative to a likelihood-based test. Our investigation provides further insight into how and why transmission-based tests and descriptive summaries can mislead about GxE. For exploring GxE, we suggest graphical displays o...Continue Reading

References

Mar 30, 1999·Genetic Epidemiology·D J Schaid
Jan 13, 2000·American Journal of Human Genetics·D M Umbach, C R Weinberg
Jun 29, 2004·The European Respiratory Journal·S L ChengP C Yang
May 26, 2007·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·K J BrookesP Asherson

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Citations

Apr 15, 2011·Epidemiology·Min ShiClarice R Weinberg

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