title: Detecting gene-environment interactions in human birth defects: Study designs and statistical methods.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Caroline G
authors.initials: CG
authors.lastname: Tai
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Graff
authors.affiliation: Institute for Human Genetics, University of California San Francisco, San Francisco, California.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Passarelli
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Mefford
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Shaw
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.|Institute for Human Genetics, University of California San Francisco, San Francisco, California.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.|Institute for Human Genetics, University of California San Francisco, San Francisco, California.|Department of Urology, University of California San Francisco, San Francisco, California.|UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California.
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
mesh_terms: D016022:Case-Control Studies; D000013:Congenital Abnormalities / Q000209:etiology*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015233:Models, Statistical; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012107:Research Design; D012307:Risk Factors
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