Extended T(2) tests for longitudinal family data in whole genome sequencing studies

Family data and rare variants are two key features of whole genome sequencing analysis for hunting the missing heritability of common human diseases. Recently, Zhu and Xiong proposed the generalized T(2) tests that combine rare variant analysis and family data analysis. In similar fashion, we developed the extended T(2) tests for longitudinal whole genome sequencing data for family-based association studies. The new methods simultaneously incorporate three correlation sources: from linkage disequilibrium, from pedigree structure, and from the repeated measures of covariates. We assess and compare these methods using the simulated data from Genetic Analysis Workshop 18. We show that, in general, the extended T(2) tests incorporating longitudinal repeated measures have higher power than the single-time-point T(2) tests in detecting hypertension-associated genome segments.