By default, the MAF upper bound is 0.05, the MAC lower bound is 1 and the CR lower bound is 0. When the burden score is created internally, a variant is deleted if its MAF is greater than the MAF upper bound or its CR is smaller than the CR lower bound. A genetic variable is excluded from analysis if its MAC is smaller than the MAC lower bound or its CR is smaller than the CR lower bound. Under the additive or dominant (recessive) model, MAC is defined as the number of subjects with at least one (two) observed mutation. There are options for the minor allele frequency (MAF) upper bound, the minor allele count (MAC) lower bound and the call rate (CR) lower bound. The T1, T5, VT, and SKAT tests under the dominant (recessive) genetic model can be obtained by using the option -dominant ( -recessive). Use the option -test to request one of the six tests (T1, T5, MB, VT, SKAT, and customized test) under the additive genetic model (default).
Otherwise, use the options -gfile and -mfile to specify the genotype file and the mapping file, respectively, for the internal creation of the burden scores. Use the option -gfile to specify the file that contains the external genetic variables. The burden score may be determined externally (default) or internally. The genetic variable pertains to the genotype in the single-variant analysis and to the burden score in the rare-variant analysis. A table in the OPTIONS section below summarizes the available analysis options for different sampling schemes. For random sampling, all traits are treated as secondary (because the sampling does not depend on any particular trait.) The sampling scheme is specified through the option -sampling. SCORE-SeqTDS performs the LS analysis on secondary quantitative traits for random sampling, case-control and case-only sampling. The LS method is the ideal choice for random sampling and is approximately correct for analyzing secondary quantitative traits in case-control or case-only studies with rare diseases. The MLE method properly accounts for trait-dependent sampling whereas the LS method does not. Both the maximum likelihood estimation (MLE) and standard least-squares (LS) methods are available. Each quantitative trait is related to a genetic variable and possibly covariates through a linear regression model. The primary trait is the trait that is used to select subjects for sequencing, and all other traits are treated as secondary. (2013) for analyzing primary and secondary quantitative traits under trait-dependent sampling. SCORE-SeqTDS is a command-line program written in the C language to implement the methods described in Lin et al.
SCORE-SeqTDS: Score Tests for Sequencing Studies with Trait-Dependent Sampling