The now-ubiquitous VCF file format requires reference alleles to be distinguished from alternate alleles, and an increasing number of software tools and pipelines do not tolerate scrambling of the two. This presents an interoperability problem for PLINK: while it was theoretically possible to handle binary data with PLINK 1.0 in a manner that preserved the reference vs. alternate allele distinction when it was originally present, with constant use of –keep-allele-order and related flags, doing so was inconvenient and error-prone, especially since the accompanying native.ped/.map and.tped/.tfam text formats had no place to store that information. PLINK 1.9’s –a2-allele flag, which can import that information from a VCF file, provides limited relief, but it is still necessary for users to fight against the program’s major/minor-allele based design.
