meta-analysis of all participating cohorts, with a properly selected level of genome-wide statistical significance to miminize the chance of false positives, is the most powerful approach to finding new genuine associations for genetic loci (25). When findings narrowly miss the pre-specified significance threshold, genotyping individuals in other independent populations provides additional evidence about the association. For findings that substantially exceed pre-established significance thresholds, the results of a CHARGE meta-analysis effectively provide evidence of a multi-study replication.
