this way is feasible even with samples genotyped on different array-based technologies10–13. A significant limitation of combining disease study cases with public controls is that unbiased results are only achieved using the intersecting set of variants genotyped across all arrays and cohorts being combined13. This limitation effectively prevents combining cohorts where the number of shared genotyped variants is too small to form the basis for imputation or to provide whole-genome coverage. An in-depth comparison of the Illumina HumanHap, Illumina OmniExpress, and Affymetrix 6.0 arrays found over 2,000,000 single nucleotide polymorphisms (SNPs) in union but only 75,000 variants that intersect across all arrays14. Additionally, reliance on array-based technology prevents use of expanding whole-genome sequencing (WGS) resources with high representation of non-European ancestry groups, like the Trans-Omics for Precision Medicine (TOPMed) program, for public controls. Being able to combine case and public control genotypes from array- and/or sequencing-based platforms opens up the increasing set of WGS resources for new GWAS. As of January 2021, there are at least 217 case-only studies containing >136,000 samples across many genotyping platforms in the database of Genetics and Phenotypes (dbGaP) (query = ‘case set[Study Design]’). As of February 2020, freeze 6a, there are >227,000 public controls
