Dissecting prenatal, postnatal, and inherited effects: ART and design

With the failure of common variants alone to explain the bulk of trait heritability, it becomes more important to understand the contribution of maternally inherited effects, prenatal effects, and postnatal environmental effects. These effects can be disentangled by studying families containing children conceived by assisted reproductive technologies (ART). We propose and develop a model that is an extension of the variance component model commonly used in pedigree analysis. Our model is flexible enough to allow any number of family members and degrees of relationship; thus, researchers can use both small and extended families simultaneously. Simulations demonstrate that our method has appropriate statistical properties and is robust to model misspecification and accurate in the presence of missing data. Most importantly, our method is able to disentangle maternally inherited effects from prenatal effects, which are confounded in traditional family studies. Our analyses also provide guidance to researchers designing studies that will use ART families to clarify genetic and environmental factors underlying traits.