Multi-trait analysis of rare-variant association summary statistics using MTAR

摘要

In this illustration, the number of variants is  = 10 and the number of traits is  = 5. The degree of heterogeneity of among-variant effects is controlled by . MTAR methods are robust to various patterns of genetic effects across variants by combining variance-component test -values from different specifications of . The degree of heterogeneity of among-trait effects is controlled by . By changing the value of , the degree of heterogeneity of among-trait effects can be weakly, moderately, or strongly dictated by genetic correlation . By setting  = 0, iMTAR and cMTAR structures assume genetic effects become completely heterogeneous and homogeneous, respectively. MTAR methods are robust to various patterns of genetic effects across traits by combining variance-component test -values from different specifications of . The cctP that combines the single-trait burden and SKAT tests -values is particularly powerful when only a small number of traits are associated with the set of rare variants. The omnibus test MTAR-O that combines iMTAR, cMTAR, and cctP is robust to all the aforementioned patterns of genetic effects across traits and variants.