Background: The National Birth Defects Prevention Study (NBDPS) contains a wealth of information on affected and unaffected family triads, and thus provides numerous opportunities to study gene-environment interactions (G×E) in the etiology of birth defect outcomes. Depending on the research objective, several analytic options exist to estimate G×E effects that use varying combinations of individuals drawn from available triads.
Methods: In this study, we discuss important considerations in the collection of genetic data and environmental exposures.
Results: We will also present several population- and family-based approaches that can be applied to data from the NBDPS including case-control, case-only, family-based trio, and maternal versus fetal effects. For each, we describe the data requirements, applicable statistical methods, advantages, and disadvantages.
Conclusion: A range of approaches can be used to evaluate potentially important G×E effects in the NBDPS. Investigators should be aware of the limitations inherent to each approach when choosing a study design and interpreting results.
Keywords: National Birth Defects Prevention Study; birth defects; case-only; congenital heart defects; family-based study; gene-environment interaction; genetic epidemiology; neural tube defects; transmission disequilibrium test.
© 2015 Wiley Periodicals, Inc.