In Kolkata, a teenager covers her face with powder before school, hoping to hide the spreading white patches on her skin. In a rural village in West Bengal, a child with albinism struggles to read under the harsh sunlight because her eyes cannot focus. Both stories are rooted in melanin, the pigment that gives skin, hair and eyes their colour.
Skin colour has always shaped identity, opportunity and even prejudice. It is also deeply embedded in politics and culture, as seen in recent debates on colourism in South Asia and in global conversations about diversity. Beyond the social narrative, scientists have been trying to uncover the underlying molecular mechanism behind it but could not answer all. Three new studies reveal how genes determine whether colour is gradually lost, as in vitiligo, or absent from birth, as in oculocutaneous albinism.
The immune system’s attack on pigment
Vitiligo is one of the most common pigmentation disorders, affecting up to two percent of the world’s population. The white patches that mark the condition are caused not by a lack of melanin production, but by the immune system mistakenly attacking melanocytes, the cells responsible for pigment.
In a recent paper in Dermatology authored by Tithi Dutta and colleagues from the University of Calcutta conducted the first large-scale meta-analysis of genetic variants linked to vitiligo across Asian populations. They reviewed 31 case-control studies, covering nearly 9,000 patients. The standout finding was a single nucleotide polymorphism (SNP), rs1800629, in the TNF-α gene.
This genetic variation, located just upstream of the tumour necrosis factor alpha gene, increases the risk of vitiligo by altering inflammatory pathways. Patients carrying the A allele had higher levels of circulating TNF-α, a cytokine known to inhibit melanocyte function and trigger immune-mediated destruction. The discovery confirms earlier reports that vitiligo often overlaps with other autoimmune conditions, including thyroid disease, type 1 diabetes and psoriasis.
A genetic fingerprint of vitiligo
What makes this finding significant is its scope. Earlier studies had shown inconsistent results across ethnic groups, with some reporting an association and others finding no link. By pooling together data and applying rigorous statistical models, the Calcutta team, under the supervision of Dr. Sengupta, clarified the picture.
Their analysis demonstrated that the TNF-α variant was consistently associated with vitiligo risk under both dominant and recessive models. In silico analysis suggested that this variant affects the binding of transcription factors, thereby changing gene expression in skin cells. Importantly, Importantly, another study in Scientific Reports, authored by Dr. Dutta and her team provides the functional details of how the significant variants associated with vitiligo contribute towards the disease causation, emphasising inflammation and pigment loss.
For patients, the result opens new doors. If therapies targeting TNF-α can be tailored, it may be possible to slow or even halt the progression of vitiligo. Such treatments already exist for conditions like rheumatoid arthritis, but their potential in dermatology remains underexplored.
The genetics of colourless skin
While vitiligo erases pigment over time, oculocutaneous albinism (OCA) prevents pigment from forming in the first place. This inherited disorder is present at birth and is caused by autosomal recessive mutations in genes critical to melanin synthesis. The consequences extend beyond skin: patients often face severe visual impairment blindness, nystagmus, and sensitivity to sunlight.
In a separate study published in Molecular Biology Reports, first author Tithi Dutta and colleagues from the University of Calcutta performed the most extensive screening of OCA patients in Eastern India to date following Dr. Sengupta’s work. Their brief report analysed 54 patients from 41 families across West Bengal, representing 16 marriage and ethnic groups.
The team sequenced three major genes known to cause OCA: TYR, OCA2 and SLC45A2. They found 12 pathogenic or likely pathogenic variants, including several novel mutations never before reported in Indian populations. Among these were a nonsense variant in SLC45A2 (p.Leu130*) and a missense variant (p.Thr302Ser) which underscores the presence of numerous uncharacterized and unknown pathogenic variants, highlighting the need for increased focus on such studies in the field.
A patchwork of genetic diversity
The study revealed striking diversity in how OCA manifests. For instance, some patients with the same TYR mutation showed different levels of residual pigmentation. One patient carried a compound heterozygous combination that left her iris pigmented, unlike others with similar genetic backgrounds.
These variations underscore the complexity of pigment biology. Even within a single ethnic group, mutations interact with other genes and environmental factors to shape the final phenotype. The team noted that nearly half of the patients screened showed no detectable mutations in the three tested genes, pointing to the existence of other unknown loci yet to be discovered. Consequently, Tithi and Dr. Sengupta and his team, comprising Mr. Saha and Mr. Dey, have undertaken whole-exome sequencing to identify novel candidates that may play a significant role in the development of albinism.
For India, where consanguinity and founder effects are common, such genetic mapping is essential. It provides a foundation for genetic counselling, carrier screening and premarital testing, all of which can reduce the burden of inherited conditions like OCA.
Melanin, immunity and stigma
At first glance, vitiligo and albinism appear very different. One is acquired and autoimmune, the other congenital and inherited. Yet both revolve around melanocytes, the tiny factories of melanin. In vitiligo, the immune system destroys them; in albinism, genetic mutations disable them.
Both conditions also intersect with social stigma. In South Asia, where skin colour can determine marriage prospects and employment opportunities, those with visible differences are often marginalised. Studies have reported high rates of depression and anxiety among vitiligo patients. Similarly, children with albinism are vulnerable to discrimination, and in parts of Africa, to violent superstition-driven attacks.
The research from India adds a crucial regional perspective. India reports the world’s highest prevalence of vitiligo and a significant number of OCA cases. By mapping the genetic landscape, these studies not only advance science but also highlight the urgent need for public education and social support.
Tying science to current events
Skin, long a symbol of identity and difference, becomes in this context a biological interface. As debates on fairness creams continue in South Asia and as colour-based discrimination faces increasing scrutiny worldwide, these studies land at a pivotal time. They remind us that skin colour is less about beauty or status and more about biology and survival.
The science shows that what society treats as superficial is in fact deeply encoded in our DNA. It also shows how fragile pigmentation can be, unravelled by a single mutation or a misfiring immune response.
The way forward
The three studies converge on a single message about both of the complex disorder: pigment biology is a window into the human genome and into society itself. Future research must broaden to include underrepresented populations so that discoveries are not limited to a few groups.
For vitiligo, the challenge is to translate genetic findings into therapies that are affordable and accessible. For albinism, the challenge is to implement genetic counselling at a community level, especially in regions with high prevalence.
The call to action is clear: science must move hand in hand with public awareness. Understanding the genes behind skin colour should not only guide treatment but also reduce stigma. After all, skin colour has too often divided humanity. Could it now, through science, become a story of connection and care?
References
Dutta, T., Sengupta, S., Adhya, S., Saha, A., Sengupta, D., Mondal, R., Naskar, S., Bhattacharjee, S., & Sengupta, M. (2024). Identification of TNF-α as major susceptible risk locus for vitiligo: A systematic review and meta-analysis study in the Asian population. Dermatology, 240(3), 376–386. https://doi.org/10.1159/000536480
Dutta, T., Ganguly, K., Saha, A., Sil, A., Ray, K., & Sengupta, M. (2024). Identifying genetic defects in oculocutaneous albinism patients of West Bengal, Eastern India. Molecular Biology Reports, 51, 818–826. https://doi.org/10.1007/s11033-024-09777-y
Dutta, T., Mitra, S., Saha, A. Ganguly, K. Pyne, T. Sengupta, M. (2022). A comprehensive meta-analysis and prioritization study to identify vitiligo associated coding and non-coding SNV candidates using web-based bioinformatics tools. Scientific Report 12, 14543. https://doi.org/10.1038/s41598-022-18766-9
