Annals of human geneticsAnn Hum GenetDissecting the Genetic Affinity Between the Orang Asli and Southeast Asian Native Populations.1121-1210.1111/ahg.70005Southeast Asia (SEA) is a region with enriched human diversity and complex population history. Despite numerous small-scale population genetics studies being carried out, the map of human migration in this landmass remains fragmentary. Notably, the genetic affinities of the Orang Asli from Peninsular Malaysia and other SEA natives have not been comprehensively assessed.In this study, publicly available genotypic datasets were gathered and imputed. The genetic relationships and ancestry make-up of 19 SEA native populations, covering Peninsular Malaysia, Indonesia, Papua New Guinea, the Philippines, Vietnam, and Andaman, were comprehended and benchmarked with 14 global populations.With ∼20 million SNPs coverage, we provided supporting evidence to (i) a possible ancient genetic link between the Andamanese, Papuan and the Philippines and Peninsular Negrito; (ii) gene flow from the ancestors of Andamanese to Papuan, and the Negrito from Peninsular Malaysia and the Philippines; (iii) different genetic structures between the island SEA (iSEA) and mainland (mSEA) populations; (iv) close genetic affinity between the Proto-Malay Seletar with the iSEA populations and (v) close genetic affinity between the Senoi Mah Meri with the Proto-Malays.To our knowledge, this study reported the highest genomic sequence coverage and the most comprehensive SEA native populations covered thus far. Our results not only have provided strong supporting evidence to the earlier hypothesis, but also novel insights into the genetic diversity of the SEA native populations.© 2025 University College London (UCL) and John Wiley & Sons Ltd.AlvinCengnataCFaculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia.Pei-MeiThamTDivision of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, IMU University, Kuala Lumpur, Malaysia.Hoi-ThungFooFDivision of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, IMU University, Kuala Lumpur, Malaysia.Calista Zhe-QingChanCDivision of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, IMU University, Kuala Lumpur, Malaysia.XinLeeLDivision of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, IMU University, Kuala Lumpur, Malaysia.Renee Lay-HongLimLFaculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia.LianDengDState Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.ShuhuaXuXState Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.Department of Liver Surgery and Transplantation Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China.School of Life Science and Technology, ShanghaiTech University, Shanghai, China.Boon-PengHohHDivision of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, IMU University, Kuala Lumpur, Malaysia.engFRGS/1/2021/STG01/UCSI/01/1Ministry of Higher Education (MOHE) Malaysia32030020National Natural Science Foundation of China32288101National Natural Science Foundation of China32270665National Natural Science Foundation of ChinaJournal Article20250629EnglandAnn Hum Genet04166610003-4800Orang Asli peopleIMHumansAsia, SoutheasternGene FlowGenetic VariationGenetics, PopulationHuman MigrationMalaysiaPolymorphism, Single NucleotideSoutheast Asian PeopleOrang AsliSoutheast Asiagenetic affinitygenome variationsnatives2025662025111202561120251212720202571462025630233ppublish4058339610.1111/ahg.70005References

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