Estimation of gene-environment interaction by pooling biospecimens.

Abstract:

:Case-control studies are prone to low power for testing gene-environment interactions (GXE) given the need for a sufficient number of individuals on each strata of disease, gene, and environment. We propose a new study design to increase power by strategically pooling biospecimens. Pooling biospecimens allows us to increase the number of subjects significantly, thereby providing substantial increase in power. We focus on a special, although realistic case, where disease and environmental statuses are binary, and gene status is ordinal with each individual having 0, 1, or 2 minor alleles. Through pooling, we obtain an allele frequency for each level of disease and environmental status. Using the allele frequencies, we develop a new methodology for estimating and testing GXE that is comparable to the situation when we have complete data on gene status for each individual. We also explore the measurement process and its effect on the GXE estimator. Using an illustration, we show the effectiveness of pooling with an epidemiologic study, which tests an interaction for fiber and paraoxonase on anovulation. Through simulation, we show that taking 12 pooled measurements from 1000 individuals achieves more power than individually genotyping 500 individuals. Our findings suggest that strategic pooling should be considered when an investigator designs a pilot study to test for a GXE.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

Danaher MR,Schisterman EF,Roy A,Albert PS

doi

10.1002/sim.5357

subject

Has Abstract

pub_date

2012-11-20 00:00:00

pages

3241-52

issue

26

eissn

0277-6715

issn

1097-0258

journal_volume

31

pub_type

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