10.1371/journal.pgen.1007640 Sijie Wu Sijie Wu Manfei Zhang Manfei Zhang Xinzhou Yang Xinzhou Yang Fuduan Peng Fuduan Peng Juan Zhang Juan Zhang Jingze Tan Jingze Tan Yajun Yang Yajun Yang Lina Wang Lina Wang Yanan Hu Yanan Hu Qianqian Peng Qianqian Peng Jinxi Li Jinxi Li Yu Liu Yu Liu Yaqun Guan Yaqun Guan Chen Chen Chen Chen Merel A. Hamer Merel A. Hamer Tamar Nijsten Tamar Nijsten Changqing Zeng Changqing Zeng Kaustubh Adhikari Kaustubh Adhikari Carla Gallo Carla Gallo Giovanni Poletti Giovanni Poletti Lavinia Schuler-Faccini Lavinia Schuler-Faccini Maria-Cátira Bortolini Maria-Cátira Bortolini Samuel Canizales-Quinteros Samuel Canizales-Quinteros Francisco Rothhammer Francisco Rothhammer Gabriel Bedoya Gabriel Bedoya Rolando González-José Rolando González-José Hui Li Hui Li Jean Krutmann Jean Krutmann Fan Liu Fan Liu Manfred Kayser Manfred Kayser Andres Ruiz-Linares Andres Ruiz-Linares Kun Tang Kun Tang Shuhua Xu Shuhua Xu Liang Zhang Liang Zhang Li Jin Li Jin Sijia Wang Sijia Wang Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans Public Library of Science 2018 Han East Asian-European admixture human eyebrow thickness SOX 2 Uyghur 3 q 26.33 signal EDAR GWAS subject genome-wide significance 2 q 12.3 Genome-wide association studies CANDELA Latin American countries 5 q 13.2 editing evidence FOXD 1 genes variant CRISPR Rotterdam Study cohort 2018-09-24 17:26:11 Dataset https://plos.figshare.com/articles/dataset/Genome-wide_association_studies_and_CRISPR_Cas9-mediated_gene_editing_identify_regulatory_variants_influencing_eyebrow_thickness_in_humans/7123484 <div><p>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 <i>SOX2</i> (rs1345417: P = 6.51×10<sup>−10</sup>) and at 5q13.2 near <i>FOXD1</i> (rs12651896: P = 1.73×10<sup>−8</sup>). 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<sup>−11</sup>) near <i>EDAR</i>. 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 <i>SOX2</i> and <i>FOXD1</i> 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.</p></div>