Background: Studies that ascertain families containing multiple relatives affected by disease can be useful for identification of causal, rare variants from next-generation sequencing data.
Results: We present the R package SimRVPedigree, which allows researchers to simulate pedigrees ascertained on the basis of multiple, affected relatives. By incorporating the ascertainment process in the simulation, SimRVPedigree allows researchers to better understand the within-family patterns of relationship amongst affected individuals and ages of disease onset.
Conclusions: Through simulation, we show that affected members of a family segregating a rare disease variant tend to be more numerous and cluster in relationships more closely than those for sporadic disease. We also show that the family ascertainment process can lead to apparent anticipation in the age of onset. Finally, we use simulation to gain insight into the limit on the proportion of ascertained families segregating a causal variant. SimRVPedigree should be useful to investigators seeking insight into the family-based study design through simulation.
Keywords: Anticipation; Ascertainment bias; Family-based study; Pedigree simulation; Rare variant.