Abstract
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.
Highlights
We identify other genes contributing to red hair, the combined effect of which accounts for ~90% of the SNP heritability
By performing genome-wide analyses across hair colours, we have discovered novel variation in and around MC1R that contributes to red hair
We identify eight additional variants that explain most of the SNP heritability of red hair, including variants at agouti signalling protein (ASIP), where an expression QTL (eQTL) shows epistatic interactions with the poorly penetrant MC1R variants
Summary
We identify more than 200 genetic variants independently associated with multiple hair colours on the spectrum of blond to black. The strongest association with red hair is located around the MC1R gene on human chromosome 16 (Fig. 1a, Supplementary Table 1, Supplementary Figure 1a), which fits with the expectation that this locus is the principal genetic factor determining red hair colour. As we know that multiple MC1R alleles affect red hair colour, we performed stepwise conditional association testing and identified 31 additional association signals in this region at genome-wide levels of statistical significance (p ≤ 5×10−8), altering the odds of having red hair compared to brown and black hair (Supplementary Table 1).
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