In the primary analytic model, low frequency and rare variants were collapsed into an aggregate low frequency variant term and aggregate rare variant term, respectively. Individuals with at least one copy of the minor allele for any of the nonsynonymous or frameshift variants were coded as 1 in each variant class (low frequency or rare), and individuals without any minor allele copies in this class were coded as 0. This collapsing method was based on a burden test24 to increase power to detect the cumulative effect of these variant classes.
