Kock K.H.Tan L.M.Han K.Y.Ando Y.Jevapatarakul D.Chatterjee A.Lin Q.X.X.Buyamin E.V.Sonthalia R.Rajagopalan D.Tomofuji Y.Sankaran S.Park M.S.Abe M.Chantaraamporn J.Furukawa S.Ghosh S.Inoue G.Kojima M.Kouno T.Lim J.Myouzen K.Nguantad S.Oh J.M.Rayan N.A.Sarkar S.Suzuki A.Thungsatianpun N.Venkatesh P.N.Moody J.Nakano M.Chen Z.Tian C.Zhang Y.Tong Y.Tan C.T.Y.Tizazu A.M.Loh M.Hwang Y.Y.Ho R.C.Larbi A.Ng T.P.Won H.H.Wright F.A.Villani A.C.Park J.E.Choi M.Liu B.Maitra A.Pithukpakorn M.Suktitipat B.Ishigaki K.Okada Y.Yamamoto K.Carninci P.Chambers J.C.Hon C.C.Matangkasombut P.Charoensawan V.Majumder P.P.Shin J.W.Park W.Y.Prabhakar S.Mahidol University2025-04-012025-04-012025-01-01Cell (2025)00928674https://repository.li.mahidol.ac.th/handle/20.500.14594/108517The relationships of human diversity with biomedical phenotypes are pervasive yet remain understudied, particularly in a single-cell genomics context. Here, we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 donors, spanning 7 population groups across 5 Asian countries, and 6 controls. Though population groups are frequently compared at the continental level, we found that sub-continental diversity, age, and sex pervasively impacted cellular and molecular properties of immune cells. These included differential abundance of cell neighborhoods as well as cell populations and genes relevant to disease risk, pathogenesis, and diagnostics. We discovered functional genetic variants influencing cell-type-specific gene expression, which were under-represented in non-Asian populations, and helped contextualize disease-associated variants. AIDA enables analyses of multi-ancestry disease datasets and facilitates the development of precision medicine efforts in Asia and beyond.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1016/j.cell.2025.02.0172-s2.0-10500048347410974172