It is widely known that people in Okinawa originated from the Jomon people, and are generally tolerant to alcohol. However, some individuals in mainland Japan lack alcohol tolerance due to a mutation in the human mitochondrial aldehyde dehydrogenase 2 (ALDH2) gene. Furthermore, the JC virus (JCV) genotype MY, which is related to the Jomon people, has not been found in Okinawa. In this study, to analyze the origin of the Okinawan people, we investigated the relationship between the JCV genotype and ALDH2 genotype. We collected 108 JCV positive samples from Okinawa. Only CY genotype JCV, and not the MY genotype, was detected. Among JCV-positive samples, a variant of ALDH2 (Glu/Lys heterozygote) was detected in 31 samples (29%) and wild-type ALDH2 (Glu/Glu homozygote) was detected in 77 samples (71%). Another variant of ALDH2 (Lys/Lys homozygote) was not detected. Among carriers of CY genotype JCV, wild-type ALDH2 was much more frequent in people living in Okinawa than in mainland Japan (P < 0.05). Our results suggested that the original inhabitants of Okinawa were people who carried MY genotype JCV and wild-type ALDH2; and that after the extinction of these original inhabitants, people who carried CY genotype JCV and wild-type ALDH2 migrated to the area. Due to the founder effect, CY genotype JCV and wild-type ALDH2 became dominant. Over a long period, many people with the variant ALDH2 migrated to Okinawa; the variant allele increased in frequency, but other JCV genotypes were eliminated.