Hair straightness/curliness is a highly heritable trait amongst human populations. Previous studies have reported European specific genetic variants influencing hair straightness, but those in East Asians remain unknown. One promising candidate is a derived coding variant of the ectodysplasin A receptor (EDAR), EDARV370A (370A), associated with several phenotypic changes of epidermal appendages. One of the strongest signals of natural selection in human genomes, 370A, has risen to high prevalence in East Asian and Native American populations, whilst being almost absent in Europeans and Africans. This striking frequency distribution and the pleiotropic nature of 370A led us to pursue if hair straightness, another epidermal appendage-related phenotype, is affected by this variant. By studying 1,718 individuals from four distinctive East Asian populations (Han, Tibetan, Mongolian, and Li), we found a significant association between 370A and the straight hair type in the Han (p = 2.90 × 10−6), Tibetan (p = 3.07 × 10−2), and Mongolian (p = 1.03 × 10−5) populations. Combining all the samples, the association is even stronger (p = 5.18 × 10−10). The effect of 370A on hair straightness is additive, with an odds ratio of 2.05. The results indicate very different biological mechanisms of straight hair in Europe and Asia, and also present a more comprehensive picture of the phenotypic consequences of 370A, providing important clues into the potential adaptive forces shaping the evolution of this extraordinary genetic variant.
Phenotypic Change 370A Allele East Asian Population Dental Morphology Native American Population
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
This project received funding support from the National Natural Science Foundation of China (31271338), Ministry of Science and Technology (2011BAI09B00), Ministry of Health (201002007), Ministry of Education (311016) to L. J.; the Packard Foundation Fellowship in Science and Engineering and an National Institutes of Health Innovator Award (1DP2OD006514-01) to P. C. S.; National Natural Science Foundation of China (31071102), Philosophy and Social Science Foundation of Shanghai (2010BZH005) to J. T.; and National Natural Science Foundation of China (31071096), National High-Tech Research and Development Program (2012AA021802) to Y. Y. We are deeply grateful to the subjects participated in this study. S.W. acknowledges support from the Max Planck Foundation and the Chinese Academy of Sciences.
Bryk J, Hardouin E, Pugach I, Hughes D, Strotmann R, Stoneking M et al (2008) Positive selection in East Asians for an EDAR allele that enhances NF-kappaB activation. PLoS One 3:e2209PubMedCrossRefGoogle Scholar
Chang SH, Jobling S, Brennan K, Headon DJ (2009) Enhanced Edar signalling has pleiotropic effects on craniofacial and cutaneous glands. PLoS One 4:e7591PubMedCrossRefGoogle Scholar
Fujimoto A, Kimura R, Ohashi J, Omi K, Yuliwulandari R, Batubara L et al (2008a) A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness. Hum Mol Genet 17:835–843PubMedCrossRefGoogle Scholar
Fujimoto A, Ohashi J, Nishida N, Miyagawa T, Morishita Y, Tsunoda T et al (2008b) A replication study confirmed the EDAR gene to be a major contributor to population differentiation regarding head hair thickness in Asia. Hum Genet 124:179–185PubMedCrossRefGoogle Scholar
Grossman SR, Shlyakhter I, Karlsson EK, Byrne EH, Morales S, Frieden G et al (2010) A composite of multiple signals distinguishes causal variants in regions of positive selection. Science 327:883–886. doi:10.1126/science.1183863PubMedCrossRefGoogle Scholar
Hitsch GJ, Hortacsu A, Ariely D (2010) What makes you click? Mate preferences and matching outcomes in online dating. Quant Mark Econ 8:393–427CrossRefGoogle Scholar
Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L et al (2013) Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell 152:691–702PubMedCrossRefGoogle Scholar
Kimura R, Yamaguchi T, Takeda M, Kondo O, Toma T, Haneji K et al (2009) A common variation in EDAR is a genetic determinant of shovel-shaped incisors. Am J Hum Genet 85:528–535PubMedCrossRefGoogle Scholar
Medland SE, Nyholt DR, Painter JN, McEvoy BP, McRae AF, Zhu G et al (2009a) Common variants in the trichohyalin gene are associated with straight hair in Europeans. Am J Hum Genet 85:750–755PubMedCrossRefGoogle Scholar
Mou C, Thomason HA, Willan PM, Clowes C, Harris WE, Drew CF et al (2008) Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form. Hum Mutat 29:1405–1411PubMedCrossRefGoogle Scholar
Park JH, Yamaguchi T, Watanabe C, Kawaguchi A, Haneji K, Takeda M et al (2012) Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits. J Hum Genet 57:508–514. doi:10.1038/jhg.2012.60PubMedCrossRefGoogle Scholar
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575PubMedCrossRefGoogle Scholar
Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E, Cotsapas C et al (2007) Genome-wide detection and characterization of positive selection in human populations. Nature 449:913–918. doi:10.1038/nature06250PubMedCrossRefGoogle Scholar