Hair color is one of the first traits you notice about a person, but its genetic underpinnings are not so obvious.
Twin studies suggest that up to 97 percent of variation in hair color is heritable, but the 13 loci associated with hair color that have been identified to date only explain about 13 percent of that heritability suggesting that many hair pigmentation genes remain undiscovered.
To fill in those gaps, a research team from King’s College, London, worked in collaboration with 23andMe on a recently published study in Nature Genetics, where they identified 124 loci significantly associated with self-reported hair color.
The team, led by Tim Spector, MD, Professor of Genetic Epidemiology and Director of the TwinsUK Registry, utilized large genomic datasets, including research participants from 23andMe (n=157,653) and the UK Biobank (n=133,238), to identify much of the missing heritability for pigmentation. Participants self-reported their natural adult hair color as one of the following categories: blond, red, light brown, dark brown, and black. In order to minimize population admixture and stratification, the analyses were adjusted for age, sex, and the first ten principal components of the genotype matrix. The analyses were also restricted to individuals of homogenous European ancestry.
The results of a genome wide association study meta analysis reached conventional genome-wide significance (p<5×10-08) in 124 loci, including all 13 previously known pigmentation loci. To validate these results and introduce a testing dataset, researchers collected GWAS summary statistics from the International Visible Trait Genetics (VisiGen) Consortium, and conducted another meta-analysis of that dataset. Despite the lower statistical power of the replication cohort due to smaller sample size, most leading SNP loci from the discovery meta-analysis replicated with the same direction of association (73 of 124 loci). Analyses also confirmed a strong association in line with the known North-South cline in hair color variation, especially in the less ethnically homogeneous 23andMe cohort.
The loci identified in this study explain 34.6 percent of red hair, 24.8 percent of blond hair, and 26.1 percent of black hair heritability, vastly improving our understanding of pigmentation in humans. While additional pigmentation genes are still yet to be discovered, this research will help guide future studies, including those on the functional mechanisms leading to pigmentation variation. These advances could ultimately lead to the discovery of treatments for diseases that result from biological impairment of pigmentation, such as melasma and vitiligo, and may aid forensic and anthropological applications of DNA-based prediction.
The full set of summary statistics can be made available to qualified investigators who enter into an agreement with 23andMe that protects participant confidentiality. Please contact [email protected] for more information.
Hysi PG, Valdes AM, Liu F, Furlotte NA, et al. “Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability.” Nature Genetics. 16 April 2018.