Genome-wide association studies (GWAS) of asthma and chronic obstructive pulmonary disease (COPD) with ever-increasing sample sizes have found multiple genetic loci associated with either disease. However, there are few intersecting loci between asthma and COPD. GWAS specifically focused on asthma–COPD overlap (ACO) have been limited by smaller sample sizes and the lack of a consistent definition of ACO that has also hampered clinical and epidemiologic studies. Other genomic techniques, such as gene expression profiling, are feasible with smaller sample sizes. Genetic analyses of objective measures of airway reactivity and allergy/T2 inflammation biomarkers in COPD studies may be another strategy to overcome limitations in ACO definitions.