PLoS Genetics (2018-09-01)

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

  • Sijie Wu,
  • Manfei Zhang,
  • Xinzhou Yang,
  • Fuduan Peng,
  • Juan Zhang,
  • Jingze Tan,
  • Yajun Yang,
  • Lina Wang,
  • Yanan Hu,
  • Qianqian Peng,
  • Jinxi Li,
  • Yu Liu,
  • Yaqun Guan,
  • Chen Chen,
  • Merel A Hamer,
  • Tamar Nijsten,
  • Changqing Zeng,
  • Kaustubh Adhikari,
  • Carla Gallo,
  • Giovanni Poletti,
  • Lavinia Schuler-Faccini,
  • Maria-Cátira Bortolini,
  • Samuel Canizales-Quinteros,
  • Francisco Rothhammer,
  • Gabriel Bedoya,
  • Rolando González-José,
  • Hui Li,
  • Jean Krutmann,
  • Fan Liu,
  • Manfred Kayser,
  • Andres Ruiz-Linares,
  • Kun Tang,
  • Shuhua Xu,
  • Liang Zhang,
  • Li Jin,
  • Sijia Wang

Journal volume & issue
Vol. 14, no. 9
p. e1007640


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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.