Cellular Complexity and Systemic Immune Profiles across Ancestral Diversity in Thailand and Mainland Southeast Asia

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Abstract
Mainland Southeast Asia (MSEA) remains under-represented in global immunogenomic references despite its extensive genetic heterogeneity. We present the first single-cell immune atlas of an MSEA population, utilizing Thai individuals from the Asian Immune Diversity Atlas (AIDA) as a representative cohort. We demonstrate that the Thai population is highly genetically diverse, reflecting its history as a geographic nexus for Asian admixture. By integrating single-cell transcriptomics with high-resolution genotyping, we show that genetic ancestry significantly shapes innate immune profiles, specifically CD14+ monocytes, highlighting potential evolutionary adaptations to regional pathogens. We identify specific sex-by-ancestry interactions that may drive the baseline activation of pro-inflammatory pathways in females, providing a long-sought cellular rationale for the high prevalence of autoimmune disorders observed in Southeast Asian populations. Ultimately, our study reveals that population-specific genetic architecture dictates immune heterogeneity often missed by self-reported ethnicity or country of origin, providing a critical immunogenomic reference for precision medicine in MSEA regions.
Funding Information
  • Program Management Unit for National Competitiveness Enhancement (PMU-C) grant (C10F650132)
  • Chan Zuckerberg Initiative (CZI) DAF, an advised fund of Silicon Valley Community Foundation grant (CZF2019-002446)
  • National Research Council of Thailand (NRCT) and Mahidol University grant (N42A670557)
  • Development and Promotion of Science and Technology Talents Project (DPST) (-)