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On the Use of Allelic Transmission Rates for Assessing Gene‐by‐Environment Interaction in Case‐Parent Trios
Author(s) -
Shin JiHyung,
McNeney Brad,
Graham Jinko
Publication year - 2010
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2010.00599.x
Subject(s) - transmission (telecommunications) , penetrance , genetics , allele , pedigree chart , biology , statistics , population , population stratification , econometrics , range (aeronautics) , evolutionary biology , demography , gene , computer science , mathematics , genotype , engineering , telecommunications , sociology , single nucleotide polymorphism , phenotype , aerospace engineering
Summary 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 G × E . Though generally invalid, such analyses continue to appear. We revisit why heterogeneity is not equivalent to G × E 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 G × E . Through simulation, we investigate the practical implications of the bias for a transmission‐based test of G × E . We find that general population characteristics distort the picture of G × E 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 G × E . For exploring G × E , we suggest graphical displays of the transmission rates within parental mating types, as they are robust to population stratification and the penetrance model.