How is "Hair Greying" encoded by the genome?
Getting grey hair is a natural process of aging. While the popularity of grey hair varies—with some people purposefully dying their hair grey and others freaking out at the slightest grey hair. Under healthy aging conditions, the onset of hair greying in European populations tends to occur before the age of 35, while greying observed under the age of 30 is usually considered to be premature hair greying. However, it has been reported that the progression of hair greying varies between different geographic populations, with Africans and Asians showing less grey hair in general, and they tend to experience the onset of hair greying about 10 years later than Europeans.
The mechanisms of hair greying appear to be very complex and may involve many different factors, such as genetics, environment, and health. However, oxidative stress seems to contribute to all of the mechanisms. In addition, a recent study has revealed the relationship between an IRF4 gene variant and hair greying. IRF4 encodes an interferon regulatory factor that interacts with the MITF transcription factor. MITF is involved in melanin synthesis and is also suggested to be engaged in MSCs maintenance through induction of the expression of the BCL2 gene, a key factor in protection against oxidative stress in melanocytes. However, the IRF4 SNP, rs12203592, explained only a small proportion of the total variation observed in greying hair.
To better understand the mechanisms and genetics of greying hair, researchers analyzed the relationships between SNPs derived from whole-exome sequencing (WES) and literature-based selected SNPs. . The study population consisted of nearly 1,000 Polish participants, including 673 males (67.4%) and 325 (32.6%) females. The mean age of all participants was 30.5. This research was conducted in two phases in which 149 samples were used as the discovery cohort for whole-exome sequencing (WES), and the remaining 849 samples were used as a replication cohort. Participants’ level of hair greying was assessed using a 6-stage classification scheme ranging from “no greying” to “totally white hair.” In total, over 77 thousand common SNPs within the targeted gene regions were subjected to WES. However, none of those SNPs reached statistical significance. Thus, 50 SNPs that met the less strict criteria were further analyzed in the replication cohort. The results of the replication cohort revealed that the G allele of rs59733750 in the KIF1A gene and the T allele of rs1127228 in the NSMCE1 gene were found to be significantly related to a decreased likelihood of grey hair when adjusted for age, sex and hair color. In addition, 2 SNPs (the T allele of rs12203592 in the IRF4 gene and the T allele of rs2361506 in the MROH2A gene) were replicated in the validation analysis among targeted SNPs reported in Adhikari et al. (2016). The IRF4 gene has been previously linked with skin aging, while mutations in KIF1A have been previously associated with disorders like spastic paraplegia 30 and hereditary neuropathy. This is particularly interesting because neuropathy is the most common complication of diabetes, which has been shown to alter the expression of KIF1A and can lead to hair follicle damage. It will be interesting for further research to elucidate the role of KIF1A in the molecular causes and mechanisms of hair greying.
All in all this study did find the effect of IRF4 gene. However, DNA variants were found to explain less than 10% of hair greying variation and seem to have a small impact on prediction. Thus, this research further supports the genetic complexity of hair greying as a trait. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/32758128/
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