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

• Autores: Wu, Sijie; Zhang, Manfei; Yang, Xinzhou; Peng, Fuduan; Zhang, Juan; Tan, Jingze; Yang, Yajun; Wang, Lina; Hu, Yanan; Peng, Qianqian; Li, Jinxi; Liu, Yu; Guan, Yaqun; Chen, Chen; Hamer, Merel A.; Nijsten, Tamar; Zeng, Changqing; Adhikari, Kaustubh; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Bortolini, María Cátira; Canizales Quinteros, Samuel; Rothhammer, Francisco; Bedoya Berrío, Gabriel; González José, Rolando; Li, Hui; Krutmann, Jean; Liu, Fan; Kayser, Manfred; Ruiz-Linares, Andres; Tang, Kun; Xu, Shuhua; Zhang, Liang; Jin, Li; Wang, Sijia
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: EYEBROW THICKNESS; ANCESTRY; CRISPR/Cas9
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Wu, Sijie. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Zhang, Manfei. Fudan University; China. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Yang, Xinzhou. Chinese Academy of Sciences; República de China. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Peng, Fuduan. Chinese Academy of Sciences; República de China
Fil: Zhang, Juan. Fudan-taizhou Institute Of Health Sciences; China
Fil: Tan, Jingze. Fudan University; China
Fil: Yang, Yajun. Fudan University; China. Fudan-taizhou Institute Of Health Sciences; China
Fil: Wang, Lina. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Hu, Yanan. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Peng, Qianqian. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Li, Jinxi. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Liu, Yu. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Guan, Yaqun. Xinjiang Medical University; China
Fil: Chen, Chen. Changzheng Hospital; China
Fil: Hamer, Merel A.. Erasmus Mc;
Fil: Nijsten, Tamar. Erasmus Mc;
Fil: Zeng, Changqing. Chinese Academy of Sciences; República de China
Fil: Adhikari, Kaustubh. Colegio Universitario de Londres; Reino Unido
Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú
Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú
Fil: Schuler-Faccini, Lavinia. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Bortolini, Maria-Cátira. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Canizales-Quinteros, Samuel. Universidad Nacional Autónoma de México, Facultad de Quimica; México
Fil: Rothhammer, Francisco. Universidad de Tarapacá de Arica; Chile
Fil: Bedoya, Gabriel. Universidad de Antioquia; Colombia
Fil: González José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina
Fil: Li, Hui. Fudan University; China
Fil: Krutmann, Jean. Leibniz Research Institute For Environmental Medicine;
Fil: Liu, Fan. Erasmus Mc; . Chinese Academy of Sciences; República de China
Fil: Kayser, Manfred. Erasmus Mc;
Fil: Ruiz-Linares, Andres. Fudan University; China. Colegio Universitario de Londres; Reino Unido
Fil: Tang, Kun. Fudan University; China. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Xu, Shuhua. Shanghaitech University; China. Chinese Academy of Sciences; República de China. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China. Fudan University; China
Fil: Zhang, Liang. Chinese Academy of Sciences; República de China. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China
Fil: Jin, Li. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China. Fudan University; China
Fil: Wang, Sijia. Chinese Academy of Sciences; República de China. Fudan University; China. Shanghai Institute For Biological Sciences Chinese Academy Of Sciences; China