Natural hair colour within European populations is a complex genetic trait. Previous work has established that MC1R variants are the principal genetic cause of red hair colour, but with variable penetrance. Here, we have extensively mapped the genes responsible for hair colour in the white, British ancestry, participants in UK Biobank. MC1R only explains 73% of the SNP heritability for red hair in UK Biobank, and in fact most individuals with two MC1R variants have blonde or light brown hair. We identify other genes contributing to red hair, the combined effect of which accounts for ~90% of the SNP heritability. Blonde hair is associated with over 200 genetic variants and we find a continuum from black through dark and light brown to blonde and account for 73% of the SNP heritability of blonde hair. Many of the associated genes are involved in hair growth or texture, emphasising the cellular connections between keratinocytes and melanocytes in the determination of hair colour.
The MC1R Gene: Red Hair and Other Characteristics
Hair colour is one of the most striking features of an individual. It is well established that red hair is due to variants in the MC1R gene. This project has two main aims. Firstly, to analyse associations between red hair and other characteristics including self-reported and prospective cancer incidence, in particular melanoma and other skin cancers, but also other diseases and characteristics. Second, to identify other genes that interact with MC1R variants and affect hair colour. Certain MC1R variants do not always cause red hair and we will identify other genes that modify MC1R function. Red hair/MC1R status is a major risk factor for skin cancer, and although the relative risk for heterozygotes is modest, as half the population are heterozygotes it has a major impact. MC1R has also been reported to play a role in pain tolerance and birth weight, although confirmatory data is needed. Anecdotes relate red hair to many characteristics, mostly fanciful. Nevertheless finding other solid associations may inform as to genetic risk for other diseases. The melanoma association has been valuable for the exploration of cellular pathways, and links to other conditions may lead to routes for prevention or therapy. There are 22,000 self-assessed red haired individuals in Biobank, and 480,000 non-red. Existing data will allow us to look for associations between red hair (assumed homozygous MC1R variant status) and a range of biological and medical characteristics. Future DNA analysis of Biobank participants will include most common MC1R variants and better defined MC1R status. Past and future skin and other cancer occurrences will be linked to MC1R status. Analysis of DNA variants throughout the genome will allow us to identify genes that modify hair colour (and other characteristics) full cohort
|Lead investigator:||Professor Ian Jackson|
|Lead institution:||University of Edinburgh|
|2901||Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability||Morgan et al||2018||Nature Communications (2018)|