TABLE 3.

Analysis of the rare variant effects on neuritic plaques in ROSMAP sequencing data

		ZIP-b		ZIP-k		TwoStage-b		TwoStage-k		ZIP-b		ZIP-k		TwoStage-b		TwoStage-k
Gene	Var. no.	π	λ	π	λ	π′	μ	π′	μ	Fisher-p	Cauchy-p	Fisher-p	Cauchy-p	Fisher-p	Cauchy-p	Fisher-p	Cauchy-p
rare var.
ADAM10	630	0.516	0.478	0.020	0.536	0.472	0.203	0.094	0.178	0.592	0.497	0.059	0.040	0.320	0.301	0.085	0.123
ACE	93	0.774	0.007	0.530	0.047	0.749	0.020	0.527	0.095	0.036	0.015	0.116	0.093	0.076	0.041	0.199	0.179
CASS4	170	0.576	0.322	0.336	0.032	0.435	0.043	0.264	0.055	0.498	0.440	0.059	0.060	0.094	0.083	0.076	0.093
CR1	492	0.250	0.135	0.564	0.047	0.153	0.021	0.513	0.001	0.148	0.177	0.123	0.095	0.022	0.038	0.004	0.002
SLC24A4	747	0.817	0.460	0.800	0.095	0.694	0.322	0.670	0.013	0.744	0.697	0.272	0.261	0.558	0.511	0.050	0.027
SORL1	660	0.179	0.669	0.654	0.213	0.025	0.395	0.505	0.068	0.374	0.352	0.414	0.388	0.055	0.048	0.149	0.130
LOF var.
FERMT2	3	0.001	0.151	0.004	0.262	0.029	0.060	0.075	0.118	0.001	0.002	0.008	0.008	0.013	0.039	0.051	0.092
NYAP1	8	0.002	0.758	0.066	0.709	0.012	0.431	0.173	0.441	0.012	0.004	0.189	0.147	0.033	0.024	0.272	0.263
PTK2B	8	0.559	0.159	0.473	0.413	0.610	0.049	0.531	0.344	0.305	0.281	0.515	0.443	0.134	0.101	0.493	0.432
SORL1	15	0.049	0.404	0.069	0.304	0.031	0.513	0.036	0.231	0.098	0.092	0.103	0.117	0.082	0.062	0.049	0.064

Note: Analyses included the individual burden and kernel tests on γ_π and γ_λ from the ZIP-b and ZIP-k methods, and ${\gamma }_{{\pi }^{\prime }}$, and γ_μ from the two-stage approach, as well as omnibus tests using Fisher-p and Cauchy-p. The upper table shows the results from the analysis on rare variants in each gene (MAF <0.002), and the lower table only for a subset of lost-of-function (LOF) rare variants. The genes with p-value <0.05 for any individual test are listed here. The smallest p-value from either individual tests or omnibus tests are italicized for each gene. Variant weight w_B = Beta(p; 1, 25) where p is the population MAF.

Abbreviations: TwoStage-b, two-stage burden test; TwoStage-k, two-stage kernel test; ZIP-b, ZIP burden test; ZIP-k, ZIP kernel.