Vitiligo Risk Alleles Vary Across Different Populations, According to Study

Genetic variation is present among patients with vitiligo, with differences noted in vitiligo-associated genes across patient populations, according to a study published in BMC Genomic Data.¹

More specifically, researchers reported that the risk alleles rs1043101 and rs10768122 in the SLC1A2 gene are notably more common in South Asian patients compared to global averages. Likewise, the intron variant rs4766578 and nonsynonymous variant rs16891982 are enriched in enriched in European and Admixed American populations.

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Background and Methods

To date, the majority of genome wide association studies have primarily related to European and East Asian populations.²

To address this disparity, researchers involved in the present study analyzed high-coverage genomic data from the 1000 Genomes Project and the IndiGen database to explore vitiligo-associated single nucleotide polymorphisms (SNPs) across a diversity of global patient populations.

The analyses focused on 64 SNPs from European and East Asian genome wide association studies, calculating genetic risk scores and assessing their distribution among various populations.

Findings

The genetic risk scores for vitiligo demonstrated similar ranges across global populations, suggesting that risk alleles identified in European and Han Chinese patient cohorts are relevant for studying vitiligo in other groups. Specifically, while South Asian ancestry, European ancestry, Admixed American ancestry 1, and IndiGen cohorts exhibited similar quartile ranges, East Asian ancestry, Admixed American ancestry 2, and African patient populations displayed wider ranges in genetic risk scores.

Risk alleles rs1043101 and rs10768122 were found to be highly enriched in South Asian populations but depleted in African populations. Another notable SNP, rs1126809, was enriched in patients of South Asian ancestry and correlated with various skin pigmentation traits.

Several risk alleles, such as rs10876864 and rs2687812, were found to be highly enriched in the African population. Conversely, rs1043101 and rs10768122 were notably depleted in this group. Additionally, risk alleles such as rs4766578 and rs10774624 were found to be depleted in patients of East Asian and African ancestry but enriched in individuals of European ancestry.

Researchers also found that many risk alleles were enriched in European populations, including rs10774624 and rs301807, suggesting a higher prevalence of vitiligo-associated genetic variants in this group. They also found specific SNPs, such as rs9926296, to be uniquely depleted in East Asian populations.

Notably, no risk alleles were enriched in the IndiGen cohort, indicating potential genetic differences or varying allele frequencies compared to other populations. SNPs rs10774624 and rs2017445 showed significant positive selection in European and South Asian populations, respectively.

In a functional annotation and ancillary analysis of 117 SNPs associated with vitiligo, researchers found that rs16891982 were notably enriched in European and Admixed American ancestry 1 populations and could be associated with skin pigmentation disorders.

Conclusions

"The comprehensive analysis of vitiligo-associated risk alleles for enrichment and depletion across diverse populations reveals intriguing patterns," according to Bharti et al. "Notably, many variants are observed to be differentially enriched/depleted in various populations which is indicative of intricate inter-population variations."

Researchers suggested that further studies of a larger, more expansive nature should be inclusive of patients of various ethnicities. These may provide further answers, as would the identification of additional vitiligo-associated SNPs through allele frequency variation.

References

1. Bharti N, Banerjee R, Achalare A, Kasibhatla SM, Joshi R. Estimation of genetic variation in vitiligo associated genes: population genomics perspective. BMC Genom Data. July 26, 2024. doi: 10.1186/s12863-024-01254-6
2. Uffelmann E, Huang QQ, Munung NS, et al. Genome-wide association studies. Nat Rev Methods Primers. 2021;1:59. 10.1038/s43586-021-00056-9 10.1038/s43586-021-00056-9