Detecting disease association with rare variants in case-parents studies

Major advances in dna sequencing technology have generated large quantities of sequence data that promote the development of statistical methods for rare variant association analyses. although many population-based case control methods have been well developed for rare variant analysis, little work focuses on family-based studies. in this paper, we extend the existing methods to test for association of rare variants with case-parents data. we investigated the influence of non-variants and effects of causal variants on max-, multi-marker test, and collapsing method, and proposed an adaptive strategy based on a difference vector. using simulations we show that the collapsing method is affected profoundly by the number of non-causal variants and different direction effects of causal variants and multi-marker test is most robust to non-causal variants and effects of causal variants. our selective-difference strategy can improve power especially for collapsing method.