Whole-exome characterization of host genetic variation in HIV-associated genes across the high-prevalence Mizo population, Northeast India.

Saurav Roy; K Lalrintluanga; Lalengkimi Ralte; Jane Ralte; Richard L Chawngthu; Sumit Aggarwal; Swagnik Roy; Nachimuthu Senthil Kumar

doi:10.1016/j.gene.2026.150334

PubMed · 42542174

Whole-exome characterization of host genetic variation in HIV-associated genes across the high-prevalence Mizo population, Northeast India.

Saurav Roy·K Lalrintluanga·Lalengkimi Ralte·Jane Ralte·Richard L Chawngthu·Sumit Aggarwal·Swagnik Roy·Nachimuthu Senthil Kumar

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Abstract

BACKGROUND: The Mizoram state of Northeast India has one of the highest HIV prevalence rates in Asia, yet the host genetic factors influencing HIV susceptibility in this Tibeto-Burman population remain uncharacterised. METHODS: We performed whole-exome sequencing using Illumina NovaSeq 6000, mean coverage 100X on 76 HIV-negative Mizo individuals. Variants were called using GATK HaplotypeCaller v4.3 against GRCh38p14, annotated with ANNOVAR, and filtered using hard-quality thresholds (QD ≥ 2, SOR ≤ 3, MQ ≥ 40, DP ≥ 10, GQ ≥ 20). The allele frequencies were compared against gnomAD v2.1.1 population databases. Hardy-Weinberg equilibrium was assessed using the Wigginton exact test with Bonferroni correction. RESULTS: Post-quality filtering resulted in 12,011 sample-variants across 2,821 unique positions from 36 HIV-associated loci (33 protein-coding genes, 2 chemokine ligands, and 3 lncRNA targets). Of these, 784 observations (51 unique positions) were high-impact nonsynonymous or loss-of-function variants. ADAR rs2229857 (p.K384R, NM_015840) was the most frequently observed variant (Mizo carrier frequency = 0.895; 95% CI: 0.806-0.946). CXCR1 rs16858808 (p.R335C) showed the greatest population enrichment (Mizo carrier frequency = 0.197; 95% CI: 0.123-0.300; 7.65-fold carrier-frequency enrichment versus gnomAD South Asian; CADD = 15.60). Sixteen of 20 tested variants deviated from Hardy-Weinberg equilibrium after Bonferroni correction (p < 0.0025), predominantly showing excess homozygosity consistent with the endogamous Mizo population. The protective variant CCR5-Δ32 was absent in all the 76 individuals tested. CONCLUSION: This first whole-exome characterization of HIV host genes in the Mizo population identifies CXCR1 rs16858808 as the most population-enriched functional variant and reveals a pervasive endogamy signature. These findings provide a population-specific genetic framework for future HIV susceptibility studies and ART pharmacogenomics research.

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Humans India HIV Infections Gene Frequency Polymorphism, Single Nucleotide Exome Sequencing Genetic Predisposition to Disease Genetic Variation Exome Prevalence South Asian People Genomics HIV genetics Mizo population Northeast India Journal Article

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Saurav Roy, K Lalrintluanga, Lalengkimi Ralte, Jane Ralte, Richard L Chawngthu, Sumit Aggarwal, Swagnik Roy, Nachimuthu Senthil Kumar. 2026-08-01. Whole-exome characterization of host genetic variation in HIV-associated genes across the high-prevalence Mizo population, Northeast India.. https://doi.org/10.1016/j.gene.2026.150334

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Journal Article resource Gene Frequency subject Genetic Predisposition to Disease subject Genetic Variation subject Genomics subject HIV Infections subject Humans subject India subject Journal Article subject Polymorphism, Single Nucleotide subject Prevalence subject

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