Extensive simulations in the sequencing setting were carried out to evaluate and compare the haplotype-based approach with the rare variant methods that drew on a more conventional collapsing strategy.
For all the tests, the collapsing strategy performed better than weighting.
For the collapsing strategy, the reduction in the number of SNPs was beneficial despite the loss of association signal from the excluded common SNPs.
Also, it is notable that across the four scenarios, the performances of the four tests were very similar under the collapsing strategy.
Under the strong effect size of rare variants when common variants were excluded from the analysis, we observed better performance of collapsing strategy and lower power of weighting pooling strategy.
Li and Leal (2008) proposed a group-wise test exploiting both multivariate and collapsing strategies that possess higher power than a simple multivariate test or simple collapsing.
To address this, we developed two collapsing strategies, one focuses rare variation collapsing on homology-based protein domains as the unit for collapsing and another gene-level approach that, unlike standard methods, leverages existing evidence of purifying selection against missense variation on said domains.
Moreover, we discovered that the magnitude of the difference in power among similarity-based methods, when applied with weighting and collapsing strategies, may be very high, sometimes over 50%.
Wagering on a collapsing regime is not a strategy that befits a major power, especially if it is accompanied by the deaths of 18 thousand people.
Swissair, which owned 49.5percentt of Sabena as part of a failed European expansion strategy, collapsed under a mountain of debt when international air passenger traffic evaporated after Sept. 11.
The strategy collapsed when a judge ordered the ballot opened up to Mr. McCain and other Republican challengers.
