METAL has been used extensively by many groups since its initial release in January 2008. This field testing enabled not only thorough debugging but improvements in error-detection methods. METAL can be run interactively or with a command script as input. Input files are processed one at a time and used to update intermediate statistics stored in memory. METAL implements Cochran's Q-test for heterogeneity (Cochran, 1954) and the appropriate statistics can be calculated if requested by the user. METAL was designed for flexible formatting of input files, and allows users to customize labels for key columns, input field delimiters and other characteristics of each input file. Information on genomic strand is used, if available, and—when it is unavailable—METAL automatically resolves strand mismatches for markers where strand is obvious (e.g. all SNPs except those with A/T and C/G alleles). METAL has an option to estimate a genomic control parameter (Devlin and Roeder, 1999) for each input file and apply an appropriate genomic control correction to input statistics prior to performing meta-analysis. To facilitate the detection of allele labels that may have been
