title: 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.
authors.affiliation: Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, U.S.A.
authors.forename: M R
authors.initials: MR
authors.lastname: Danaher
authors.forename: E F
authors.initials: EF
authors.lastname: Schisterman
authors.forename: A
authors.initials: A
authors.lastname: Roy
authors.forename: P S
authors.initials: PS
authors.lastname: Albert
mesh_terms: D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase / Q000097:blood; D056808:Biostatistics / Q000379:methods*; D016022:Case-Control Studies; D015331:Cohort Studies; D004043:Dietary Fiber / Q000008:administration & dosage; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008597:Menstrual Cycle / Q000097:blood / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D015999:Multivariate Analysis; D011446:Prospective Studies; D018401:Sample Size; D055815:Young Adult
chemical_list: D004043:Dietary Fiber; D012739:Gonadal Steroid Hormones; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human