Using offspring-parent triads to study complex traits: A tutorial based on orofacial clefts

Abstract

Health investigators routinely collect DNA and environmental data from study participants in order to assess the impact of genetic and environmental risk factors on an outcome of interest. When planning a study, alternate study designs are evaluated to minimize bias and achieve a large enough sample size from available resources. With the enormous volumes of high-quality biomedical data housed within its numerous biobanks, Norway is particularly well-suited to spearhead the investigation of a wide array of exposures and outcomes in a systematic manner. The rich array of longitudinal phenotypic data also permits an assessment of geneenvironment- timing interactions. Maximizing the research potential inherent in Norwegian biobanks is the overarching aim of Biobank Norway, an infrastructure project recently funded by the Norwegian Research Council. The development of advanced statistical tools for the analysis of high-throughput genomic data is critical to fulfill this aim and biostatistics platforms have been key elements of major biobank harmonization initiatives. However, many of these approaches have focused on traditional case-control designs. To exploit the particular advantages inherent in the Norwegian Mother and Child Cohort Study (MoBa), we describe here models to analyze the special data configurations available with offspring-parent designs. These models and the statistical tools outlined in this review were developed through the support of Biohealth Norway, a biobank platform funded by the Norwegian Functional Genomics Research Program (FUGE).