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Advancement in sequencing technology enables the study of association betweencomplex disorders and rare variants with low minor allele frequencies. One ofthe major challenges in rare variant testing is lack of statistical power oftraditional testing methods due to extremely low variances of single nucleotidepolymorphisms. In this paper, we introduce a W-test collapsing method thatevaluates the distributional differences in cases and controls using a combinedlog of odds ratio. The proposed method is compared with the Weighted-SumStatistic and Sequence Kernel Association Test using simulation data sets andshowed better performances and faster computing speed. In the study of realnext generation sequencing data set of hypertensive disorder, we identifiedgenes of interesting biological functions that are associated to metabolismdisorder and inflammation, which include the MACROD1, NLRP7, AGK, PAK6 andAPBB1. The W-test collapsing method offers a fast, effective and alternativeway for rare variants association analysis.

A W-test collapsing method for rare variant testing with applications to exome sequencing data of hypertensive disorder