biostudies-literatureEdahiro RMEXT | Japan Society for the Promotion of Science (JSPS)Japan Agency for Medical Research and Development (AMED)1905-1921https://www.ebi.ac.uk/biostudies/studies/S-EPMC12339405biostudies-literatureUnknown57(8)Current molecular quantitative trait locus catalogs are mostly at bulk resolution and centered on Europeans. Here, we constructed an immune cell atlas with single-cell transcriptomics of >1.5 million peripheral blood mononuclear cells, host genetics, plasma proteomics and gut metagenomics from 235 Japanese persons, including patients with coronavirus disease 2019 (COVID-19) and healthy individuals. We mapped germline genetic effects on gene expression within immune cell types and across cell states. We elucidated cell type- and context-specific human leukocyte antigen (HLA) and genome-wide associations with T and B cell receptor repertoires. Colocalization using dynamic genetic regulation provided better understanding of genome-wide association signals. Differential gene and protein expresNature geneticsDeciphering state-dependent immune features from multi-layer omics data at single-cell resolution.PMC1233940522gm1810003h000122H00476, 24K02697Saito ROsawa TSaito YMiyazaki YTanino YMotooka DIhara SSonehara KWatanabe CHosoda CMashimo SOgata TTakayanagi NWatanabe HIsogai SWatanabe MWatanabe KUchida TTsuburai TFukuyama SUchida SKita TKashiwada TYatomi MKuse NKanda HKagyo JNishitsuji MMorisaki HJapan COVID-19 Task ForceSaito FSaito HHanada SKan-O KKishi HMakino YAsano KYamasaki MSato YMakino SNaito TNamkoong HKimizuka YChubachi SHashimoto SMiyano SUchimura YIshikura HHashimoto NKaneko YOgata HOhta SKuramochi MNanki KUwamino YImamura TOhta KSato TSato RYamashita TSato MSato GKuge TMatsuse HKusaka YWakahara KShirai YTone MChiba SYonekawa AOta SSakurai TNakamura MKitagawa YNakamura KAnzai TTsuchida TEdahiro RIshiguro TIshioka KKojima MOchi JNakamura ATateno HAbe RAzuma MAbe SNakamura YOkamori SNakada TAKasamatsu YNagai HHyugaji TKohashi STateishi TMori NSagara HHorinouchi HOgura TYoneda MMatsunaga TIzumo THarada YHarada SOgura SHarada NHarada MMuranaka HKomuta KBeppu SHashiguchi MHagimoto SMiyazaki MMotegi MTakaoka HOdani TShimada THiramatsu YOgawa AHirano TOshima TShimada HSugimoto HKawana AKumanogoh AFujimoto NKishikawa TSassa CTKoike RKawana MHagihara MShibusawa TKimura AOgawa SAmishima MNishi KHirouchi TFunatsu YHaruta YKimura YSasa NKimura TNannya YWakabayashi AMorita TKimura NSueyoshi AMorita AShibata SMasuda MKai HAzekawa SShibata YKuwahara NYoshihara TOkamoto MIshii MKawashima HYoshida SNagasaki TYoshida TYoshida EFujita KYoshida KNamba SNagasaki YIshii TEriguchi YKikuchi RFujii KUtsugi MOshio TKagaya TEnomoto TKobayashi KTakano KFukui TNiitsu THoshino KTakano TFukui YTogashi YIgarashi ANishikawa MHasegawa TEgi MHasegawa YManabe TNoda YTakada MTada AEndo MSonobe KShimizu TShimizu EEndo ATakahashi YTakahashi TIwagoe HNakayama STakahashi SHasegawa NTakahashi MTakahashi KTakahashi HMatsumoto SMatsumoto TKamimaki IMurohashi KAwano NFujiwara ANagata KMatsui YMiyawaki MKobayashi YMatsumoto KShimo MNakamori YKawamura KMutoh YOzaki SOno YYamagata KMaruyama SSandhu YSano TMinemura HAsakura TSageshima HKamata HLiu YCInoue TInoue SEguchi HShinozuka JShinozuka KYamada MAmiya SOyamada YIchimura NYamada YSano HIshihara SInoue YSasaki JSasaki KSado RSado TKonishi SNagao GOdate MShoko TNakano YKozu YFuke SAi MSaiki RChihara YNishio KMiyazawa NYokote KNakano CIzumi NNukaga SNishiyama KYamano YHiki MKomase YKodaka NFukunaga KHonda TYasui YHiranuma HSakagami SKuraki TTakagi HAndo AOhba TYoshifuji AInomata MYoshiya KWada STanaka HMaeda SSugiura HTakeuchi MOmae YSekikawa YIchikado KTanaka AUeno TShiomi TTomono KSakakibara SWada DTominaga YNakatsumi HOguma TMitamura KOhira YArimura KTohda SSuzuki SShichinohe YSatomi RHayashi SSuzuki JSuzuki KShiroyama THayashi RKaneyama YUeda KYagi KMurakami KKokuto HSuzuki YKoh HHagiwara SMurakami THida NFuchimoto YKawada MSuematsu RHagiwara EUeda SUeda TOkabayashi HMaeno THayashi KOno HMaruyama JNishida TShinoki MHase ITaki ROno AGon YYoshiyama TTokunaga YOnoi KDoki YKanai TKurihara YTakoi HHirai YTakita MMiyagawa KKanai MIchikawa MWang QSHashino TArai DNarumoto OSeike MLee HOmote NKatayama KTanaka YHara RTanaka TAdachi YTerashima MAdachi TTokunaga KUno SNagasaka TIkemura STakei RFukuta TArai SArai RKono YTakaku YKoji SIto YTerai HFujitani SIto SKamiya AMasuzawa KIto FKoshida KNakachi IIto KNishimura TIto AYamamoto KBaba HYamamoto MNakajima JTagaya EIsono TNakajima YBaba RMasaki KBaba TYamamoto YKodama NUmeda AHirata HIwamura HShimoda MNarita ATakata THattori TNoguchi YKanaoka KNiwa KAnan RUemura MYamaguchi YKanayama SOkuzaki DKato KTani MOyama BMatsushita YImoto SSasano HMochimaru TMorikawa DKato YIshikawa MOoshima NKitamura HTomofuji YTakeda YKanehiro AOkada YKabata HNikaido TArakawa KOkada TMiyake TTakuwa AfalseDeciphering state-dependent immune features from multi-layer omics data at single-cell resolution.Current molecular quantitative trait locus catalogs are mostly at bulk resolution and centered on Europeans. Here, we constructed an immune cell atlas with single-cell transcriptomics of >1.5 million peripheral blood mononuclear cells, host genetics, plasma proteomics and gut metagenomics from 235 Japanese persons, including patients with coronavirus disease 2019 (COVID-19) and healthy individuals. We mapped germline genetic effects on gene expression within immune cell types and across cell states. We elucidated cell type- and context-specific human leukocyte antigen (HLA) and genome-wide associations with T and B cell receptor repertoires. Colocalization using dynamic genetic regulation provided better understanding of genome-wide association signals. Differential gene and protein expres2025-01-01T00:00:00Z2025 Aug2026-05-29T16:34:06.001Z2026-04-08T05:23:39.044ZS-EPMC123394054072153110.1038/s41588-025-02266-3