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Testing gene‐environment interactions in family‐based association studies using trait‐based ascertained samples
Author(s) -
Zhang Weiming,
Langefeld Carl D.,
Grunwald Gary K.,
Fingerlin Tasha E.
Publication year - 2013
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.5930
Subject(s) - type i and type ii errors , trait , statistics , gene–environment interaction , computer science , gene , sample size determination , genetic association , genetics , biology , econometrics , computational biology , mathematics , genotype , single nucleotide polymorphism , programming language
The study of gene‐environment interactions is an increasingly important aspect of genetic epidemiological investigation. Historically, it has been difficult to study gene‐environment interactions using a family‐based design for quantitative traits or when parent‐offspring trios were incomplete. The QBAT‐I provides researchers a tool to estimate and test for a gene‐environment interaction in families of arbitrary structure that are sampled without regard to the phenotype of interest, but is vulnerable to inflated type I error if families are ascertained on the basis of the phenotype. In this study, we verified the potential for type I error of the QBAT‐I when applied to samples ascertained on a trait of interest. The magnitude of the inflation increases as the main genetic effect increases and as the ascertainment becomes more extreme. We propose an ascertainment‐corrected score test that allows the use of the QBAT‐I to test for gene‐environment interactions in ascertained samples. Our results indicate that the score test and an ad hoc method we propose can often restore the nominal type I error rate, and in cases where complete restoration is not possible, dramatically reduce the inflation of the type I error rate in ascertained samples. Copyright © 2013 John Wiley & Sons, Ltd.