title: Genome-wide scans reveal variants at EDAR predominantly affecting hair straightness in Han Chinese and Uyghur populations.
abstract: Hair straightness/curliness is one of the most conspicuous features of human variation and is particularly diverse among populations. A recent genome-wide scan found common variants in the Trichohyalin (TCHH) gene that are associated with hair straightness in Europeans, but different genes might affect this phenotype in other populations. By sampling 2899 Han Chinese, we performed the first genome-wide scan of hair straightness in East Asians, and found EDAR (rs3827760) as the predominant gene (P = 4.67 × 10-16), accounting for 3.66 % of the total variance. The candidate gene approach did not find further significant associations, suggesting that hair straightness may be affected by a large number of genes with subtle effects. Notably, genetic variants associated with hair straightness in Europeans are generally low in frequency in Han Chinese, and vice versa. To evaluate the relative contribution of these variants, we performed a second genome-wide scan in 709 samples from the Uyghur, an admixed population with both eastern and western Eurasian ancestries. In Uyghurs, both EDAR (rs3827760: P = 1.92 × 10-12) and TCHH (rs11803731: P = 1.46 × 10-3) are associated with hair straightness, but EDAR (OR 0.415) has a greater effect than TCHH (OR 0.575). We found no significant interaction between EDAR and TCHH (P = 0.645), suggesting that these two genes affect hair straightness through different mechanisms. Furthermore, haplotype analysis indicates that TCHH is not subject to selection. While EDAR is under strong selection in East Asia, it does not appear to be subject to selection after the admixture in Uyghurs. These suggest that hair straightness is unlikely a trait under selection.
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.
authors.forename: Sijie
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China.
authors.forename: Jingze
authors.initials: J
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225300, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.|State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China.
authors.forename: Manfei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.
authors.forename: Jinxi
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Lu
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.
authors.forename: Haiyi
authors.initials: H
authors.lastname: Lou
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.
authors.forename: Qidi
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biochemistry, Preclinical Medicine College, Xinjiang Medical University, Urumqi, 830011, China.
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Biochemistry, Preclinical Medicine College, Xinjiang Medical University, Urumqi, 830011, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Preclinical Medicine College, Xinjiang Medical University, Urumqi, 830011, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Organismic and Evolutionary Biology, Center for Systems Biology, Harvard University, Cambridge, MA, 02138, USA.|The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
authors.forename: Pardis
authors.initials: P
authors.lastname: Sabeti
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Dusseldorf, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China.|State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China. lijin.fudan@gmail.com.|State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China. lijin.fudan@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China. xushua@picb.ac.cn.|State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China. xushua@picb.ac.cn.|School of Life Science and Technology, ShanghaiTech University, Shanghai, 200031, China. xushua@picb.ac.cn.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China. wangsijia@picb.ac.cn.|State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China. wangsijia@picb.ac.cn.
authors.forename: Sijia
authors.identifier: http://orcid.org/0000-0003-4087-4274
authors.initials: S
authors.lastname: Wang
mesh_terms: D000941:Antigens / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002681:China; D053339:Edar Receptor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006197:Hair / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D006239:Haplotypes; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D000941:Antigens; C506008:EDAR protein, human; D053339:Edar Receptor; D007381:Intermediate Filament Proteins; C479420:TCHH protein, human