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PLoS Genet. 2018 Sep 24;14(9):e1007640. doi: 10.1371/journal.pgen.1007640. eCollection 2018 Sep.

Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans.

Author information

1
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
2
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, China.
3
Human Phenome Institute, Fudan University, 825 Zhangheng Road, Shanghai, China.
4
CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
5
SIBS (Institute of Health Sciences) Changzheng Hospital Joint Center for Translational Research, Institutes for Translational Research (CAS-SMMU), Shanghai, China.
6
Key laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
7
Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
8
Department of Biochemistry, Preclinical Medicine College, Xinjiang Medical University, Urumqi, China.
9
Department of Stomatology, Chang Zheng Hospital, Second Military Medical University, Shanghai, China.
10
Department of Dermatology, Erasmus MC University Medical Center Rotterdam, CA Rotterdam, The Netherlands.
11
Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, United Kingdom.
12
Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
13
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre Brasil.
14
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica, México City, México.
15
Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile.
16
Laboratorio de Genética Molecular (GENMOL), Universidad de Antioquia, Medellín, Colombia.
17
Instituto Patagónico de Ciencias Sociales y Humanas, Centro Nacional Patagónico, CONICET, Puerto Madryn, Argentina.
18
IUF-Leibniz Research Institute for Environmental Medicine, Dusseldorf, Germany.
19
Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, CA Rotterdam, The Netherlands.
20
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
21
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming China.

Abstract

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10(-10)) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10(-8)). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10(-11)) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.

PMID:
30248107
PMCID:
PMC6171961
DOI:
10.1371/journal.pgen.1007640
[Indexed for MEDLINE]
Free PMC Article

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