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Monogenic mutations have been found in a low percentage of patients, and multifactorial or polygenic inheritance may be involved in unsolved patients. In the complex disease model, the epistatic effect of multiple variants in several genes and environmental factors such as infections may contribute. Epigenetic modifications, such as DNA methylation changes, are also proposed to be involved in CVID pathogenesis. In general, the pathogenic mechanism and molecular basis of CVID disease are still unknown, and identifying patterns of association across the genome in polygenic models and epigenetic modification profiles in CVID requires more studies. 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