Table 2.

Results of gene-based rare variants tests.

Gene	Nonsynonymous		Damaging
	MAF ≤ 0.1%	MAF ≤ 1%	MAF ≤ 0.1%	MAF ≤ 1%
FRMPD3	4.00 × 10−6	3.27 × 10−2	5.20 × 10−5	4.00 × 10−6
Number of genes	8782	10872	3017	4201
P-value threshold	5.69 × 10−6	4.60 × 10−6	1.66 × 10−5	1.19 × 10−5

After adjusting for the number of genes in each group, significant P-values are presented in bold-face.

We used the ACAT method for P-values, which first converts the P-values from the CMC, SKAT, SKATO, and VT methods to Cauchy variables, and then uses their weighted sum as the test statistic to analyze significance.

The four categories were MAF (≤0.1% and ≤1%) and functional prediction (non-synonymous and damaging variants).

MAF minor allele frequency, ACAT aggregated Cauchy association test, CMC combined multivariate and collapsing, SKAT sequence kernel association test, SKATO optimized SKAT, VT variable threshold, FRMPD3 FERM and PDZ domains containing 3.