Department of Anthropology, University of Toronto at Mississauga, Mississauga, Ontario, Canada.
Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
Commun Biol. 2021 Nov 4;4(1):1253. doi: 10.1038/s42003-021-02764-0.
Hair colour is a polygenic phenotype that results from differences in the amount and ratio of melanins located in the hair bulb. Genome-wide association studies (GWAS) have identified many loci involved in the pigmentation pathway affecting hair colour. However, most of the associated loci overlap non-protein coding regions and many of the molecular mechanisms underlying pigmentation variation are still not understood. Here, we conduct GWAS meta-analyses of hair colour in a Canadian cohort of 12,741 individuals of European ancestry. By performing fine-mapping analyses we identify candidate causal variants in pigmentation loci associated with blonde, red and brown hair colour. Additionally, we observe colocalization of several GWAS hits with expression and methylation quantitative trait loci (QTLs) of cultured melanocytes. Finally, transcriptome-wide association studies (TWAS) further nominate the expression of EDNRB and CDK10 as significantly associated with hair colour. Our results provide insights on the mechanisms regulating pigmentation biology in humans.
头发颜色是一种多基因表型，由位于毛囊中的黑色素的数量和比例差异引起。全基因组关联研究（GWAS）已经确定了许多参与影响头发颜色的色素生成途径的基因座。然而，大多数相关基因座与非蛋白编码区域重叠，并且许多色素变异的分子机制仍未被理解。在这里，我们对一个由 12741 名欧洲血统的加拿大人组成的队列进行了头发颜色的 GWAS 荟萃分析。通过进行精细映射分析，我们确定了与金发、红发和棕色头发颜色相关的色素生成基因座的候选因果变异。此外，我们观察到几个 GWAS 命中与培养黑素细胞的表达和甲基化数量性状基因座（QTL）的共定位。最后，全转录组关联研究（TWAS）进一步将 EDNRB 和 CDK10 的表达确认为与头发颜色显著相关。我们的研究结果为人类色素生成生物学的调控机制提供了新的见解。
