We also observe a good collapse of the data for the different size systems using the collapsing method of Girard et al. (2010) (Figure 6) and obtained similar values of γ=1.2 and α=1.6.
Specifically, the genetic score was defined as an indicator
To do this, other available methods would require some bioinformatic filtering in addition to the collapsing method.
For comparison purposes with the collapsing method, we only include variants with MAF <0.05 in the KBAT.
The power gain using WSS and VT versus the collapsing method without weights increases with the increase in proportion of causal variants.
Many strategies have been developed to analyze disease-associated rare variants, e.g. the collapsing method [ 14, 15], the weighted approach [ 16– 18], and regression-based analysis [ 19, 20].
Thus, the collapsing method is in fact identical to the union test (under dominant coding) by construction and power is equivalent for both tests.
We also compared the union test to the collapsing method [ 3], a set-based test for rare variant analysis that collapses the data into a X2 test with one degree of freedom.
In simulation studies comparing the maximum weighted-sum statistic from the replication-based strategy with the collapsing method of Li and Leal [ 3] and the weighted-sum statistic of Browning and Browning [ 7], the maximum test statistic consistently attained the highest power.
The collapsing method is thus a special case of the union test, with the union test applicable across the entire range of frequencies and across the entire range of linkage disequilibrium.
