One straightforward approach might be to apply a locus-specific multiple-testing correction, according to GSV complexity, to reflect the number of independent tests made at a locus, in a manner similar to that used to correct for multiple tests of SNPs in linkage disequilibrium [40]. Alternatively, more sophisticated methods developed for aggregating rare sequence variants in the absence of prior information, for instance as implemented in the ‘thgenetics’ R package [41], might be adapted for use with complex GSVs.
