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A case-control mother-child pair design is popular for genetic association studies of obstetric or neonatal outcomes because it allows assessment of both maternal and offspring genotype effects. But a practical constraint is the high genotyping cost, which may double that for a study with the same number of unrelated cases and controls. This issue is particularly relevant for genome-wide association studies, despite the decreasing genotyping cost. Here, we developed cost-effective genotyping strategies for the case-control mother-child pair design. We assumed that the maternal genome had been genotyped a priori, and that the primary goal was to detect marginal offspring genotype effects. Our results indicated that only offspring of case mothers needed to be genotyped in order to achieve a statistical power similar to that for screening the maternal genome. Our conclusion was based on a novel score statistic for testing offspring genotype effects that has a higher power than the Armitage trend test.

Design cost-effective genome-wide and candidate gene association studies of mother-child pairs