While incorporating public controls to maximize the utility of genetic discovery is desirable, there is no established approach to validly combine array- and sequencing-based genotype data. Each of these technologies has its own strengths, weaknesses, and different inter- and intra-technology measurement properties that complicate combining data across technologies. Here, we developed a protocol, Genotype Array-WGS Merge (GAWMerge), to combine genotypes from array and WGS to conduct GWAS analyses. We illustrate our protocol’s validity and its utility using TOPMed WGS samples as public controls combined with case-only array-genotyped data for GWAS of the Chronic Obstructive Pulmonary Disease (COPD) phenotype. COPD has well-established GWAS hits, therefore easily testing replication of signal, and it has high sample size for both European-ancestry and African-ancestry groups within the TOPMed program.
