Incorporating molecular genetic variation and environmental exposures into epidemiologic studies of congenital anomalies.

Epidemiologic studies of congenital anomalies rarely incorporate measurements of both environmental and genetic factors. Given the suspected etiologic heterogeneity that exists among congenital anomalies, focusing on only environmental or on only genetic factors may substantially decrease the likelihood for identifying either type of factor as a contributor to the risk of congenital anomalies. Incorporating information on genotypic variation into an epidemiologic study of environmental exposures may potentially lead to improvements in case classification with accompanying potential improvements in risk estimation. Such genotypic information may also lead to a clearer understanding of the underlying pathogenesis and etiology of congenital anomalies. Using recent research findings on congenital anomalies, we illustrated the issues of case classification and how a clearer impression of the underlying pathogenesis can be achieved with the addition of genotypic information to epidemiologic studies of congenital anomalies.