NEW YORK (GenomeWeb) – Through a genome-wide association study, a University College London-led team of researchers has linked a number of hair traits — including graying and unibrows — to certain gene variants.
The team performed a GWAS that drew on more than 6,000 people from Latin America to find 18 association signals linked to facial and scalp hair traits, as they reported today in Nature Communications. In particular, they linked a mutation in the PRSS53 gene to hair shape and found that it altered how the enzyme the gene encodes is processed and secreted. In addition, the team reported that these hair-related genomic regions are enriched for signs of selection.
"It has long been speculated that hair features could have been influenced by some form of selection, such as natural or sexual selection, and we found statistical evidence in the genome supporting that view," first author Kaustubh Adhikari from UCL said in a statement. "The genes we have identified are unlikely to work in isolation to cause graying or straight hair or thick eyebrows, but have a role to play along with many other factors yet to be identified."
Adhikari and his colleagues assessed the head and facial hair attributes of 6,630 people from the CANDELA cohort from Brazil, Colombia, Chile, Mexico, and Peru. These attributes included scalp hair shape or curliness, color, balding, and graying in men and women; and beard thickness, monobrow, and eyebrow thickness in only men.
The researchers genotyped the members of that cohort at some 9 million SNPs. The cohort had average autosomal admixture proportions of 48 percent European, 46 percent Native American, and 6 percent African, though with wide inter-individual variation. About 46 percent of the cohort was male and 54 percent was female.
After performing genome-wide tests, the researchers noted that all the traits they scored exhibited some genome-wide significant association.
In particular, Adhikari and his colleagues linked scalp hair shape and beard thickness to SNPs in 2q12. Both eyebrow thickness and unibrows were also associated with SNPs in this region.
These SNPs, the researchers noted, overlap the EDAR gene, which is part of the EDA-EDAR-EDARADD signaling pathway. During prenatal development, this pathway helps establish where hair follicle, teeth, and glands are located and what they look like. In particular, the researchers found a SNP — rs3827760 — that codes for a substitution in EDAR that's previously been linked to hair shape in East Asians.
The researchers further noted that an earlier study of the CANDELA cohort found an association between hair shape and a SNP in EDAR that's in strong linkage disequilibrium with rs3827760 in the 1000 Genomes dataset.
They further linked SNPs in FOXL2 gene region to eyebrow thickness, SNPs in 2q36 to monobrow, and SNPs in IRF4 to hair graying, among others.
"We already know several genes involved in balding and hair color, but this is the first time a gene for graying has been identified in humans, as well as other genes influencing hair shape and density," Adhikari noted.
Scalp hair shape, he and his colleagues reported, was also linked to variations in the protease serine S1 family member 53 (PRSS53) gene. In particular, the rs11150606 SNP that encodes an R30Q substitution appears to be linked to straight hair.
Through western blot analysis, the researchers found that the version of the PRSS53 protein with the R30Q substitution had a slightly different signal peptide processing and appears to have an extra proteolytic cleavage. It further is highly expressed in the hair follicle and particularly within the inner root sheath, where the researchers say it likely shapes growing hair fibers.
"[T]his new genetic variation, associated with straight hair in East Asians and Native Americans, supports the view that hair shape is a recent selection in the human family," co-author Desmond Tobin from the University of Bradford added in a statement.
The researchers searched for additional evidence of selection among gene regions associated with hair traits. They turned to the Composite of Multiple Signals (CMS) statistic that was calculated in the reference East Asian, European, and African populations from the 1000 Genomes Project data and found higher CMS scores in hair trait-related regions as compared to the genome as a whole.
In particular, they noted a selection signal in Asians in PRSS53 region SNPs as well as in the EDAR region, both linked with hair shape.