Hair morphology is one of the most differentiated traits among human populations. Genetic backgrounds of hair morphological differences among populations, however, have not yet been clarified. In addition, little is known about the evolutionary forces that have acted on hair morphology. To identify hair morphology determining genes, the levels of local genetic differentiation in 170 genes that are related to hair morphogenesis were evaluated by using data from the International HapMap project. Among highly differentiated genes ectodysplasin A receptor (EDAR), harboring an Asian-specific non-synonymous single nucleotide polymorphism (1540T/C, 370Val/Ala), was identified as a strong candidate. To examine the association between hair morphology and these candidate genes, we gathered hair and DNA samples in Thailand (Thai-Mai ethnic group), Indonesia and Japanese populations, and revealed that the Asian-specific 1540C allele is strongly associated with increase in hair thickness (multiple regression analysis considering age, sex and population; P-value = 3.8´10-10). Reporter gene assays suggested that 1540T/C affects the activity of the downstream transcription factor NF-kB. It was inferred from geographic distribution of 1540T/C and the long-range haplotype test that 1540C arose after the divergence of Asians and Europeans and its frequency has rapidly increased in East Asian populations. These findings lead us to conclude that EDAR is a major genetic determinant of Asian hair thickness and the 1540C allele spread through Asian populations due to positive selection. Recent studies revealed that 1540T/C is also associated with Asian teeth shape and that enhancement of Edar activity causes change in hair and several glands morphology in mice. Although the selective pressure that has acted on 1540C is still not clear, the polymorphism in EDAR may play a key roll in the adaptation of Asian ancestors to their environments.