A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.
Hair morphology is one of the most differentiated traits among human populations. However, genetic backgrounds of hair morphological differences among populations have not been clarified yet. 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. Association studies between genotypes and hair morphology revealed that the Asian-specific 1540C allele is associated with increase in hair thickness. Reporter gene assays suggested that 1540T/C affects the activity of the downstream transcription factor NF-kappaB. It was inferred from geographic distribution of 1540T/C and the long-range haplotype test that 1540C arose after the divergence of Asians from 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 recent positive selection.
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo, Japan.
Akihiro
A
Fujimoto
Ryosuke
R
Kimura
Jun
J
Ohashi
Kazuya
K
Omi
Rika
R
Yuliwulandari
Lilian
L
Batubara
Mohammad Syamsul
MS
Mustofa
Urai
U
Samakkarn
Wannapa
W
Settheetham-Ishida
Takafumi
T
Ishida
Yasuyuki
Y
Morishita
Takuro
T
Furusawa
Minato
M
Nakazawa
Ryutaro
R
Ohtsuka
Katsushi
K
Tokunaga
D000483:Alleles; D044466:Asian People; D053339:Edar Receptor / Q000235:genetics*; D019143:Evolution, Molecular; D005787:Gene Frequency; D006197:Hair; D006801:Humans; D009024:Morphogenesis / Q000235:genetics*; D011110:Polymorphism, Genetic
C506008:EDAR protein, human; D053339:Edar Receptor