A large Canadian cohort provides insights into the genetic architecture of human hair colour

Frida Lona-Durazo et al. perform a GWAS of human hair colour in a Canadian population cohort collected across multiple provinces. By combining these results with transcriptomic and methylation data, the authors provide further insight into the underlying biology of hair colour. 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.

Automated summary

A GWAS study of human hair color in a Canadian population identified candidate causal variants associated with blonde, red, and brown hair color. Colocalization of GWAS hits with expression and methylation QTLs of cultured melanocytes was observed. Additionally, TWAS identified the expression of EDNRB and CDK10 as significantly associated with hair color.