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We used a nested case-control study with a 2-yr prospective observation period to examine whether genetic variation is associated with BCG-induced innate immune responses and susceptibility to pediatric TB (N\u2009=\u2009134 cases, 516 controls) in BCG-vaccinated infants. Whole blood collected at 10 wk of age from 189 control infants was stimulated with BCG or media and examined with flow cytometry to measure BCG-induced PDL1, CD40, and cytokine expression in myeloid (mDC) and plasmacytoid (pDC) dendritic cells, monocytes, and neutrophils. We used a cellular and clinical GWAS to assess for associations between genetic variants, BCG-induced innate immune responses, and susceptibility to TB. We identified 11 lead genetic variants at genome-wide level significance associated with BCG-induced cytokine and surface expression markers including PDL1 (5 pDCs, 3 mDCs, 1 monocytes), CD40 (1 mDCs), and IL-6 (1 monocytes). An IGLL1 variant (rs2096522) was associated with mDC CD40 expression (P\u2009=\u20091.6e\u221208) and was also discovered as a significant variant using a gene-based method. In the clinical GWAS, we identified 39 lead variants mapping to 74 genes suggestive of an association with susceptibility to pediatric TB (P\u2009&amp;lt;\u20091e\u221205), but no variant reached genome-wide significance. One clinical lead variant in the PDE8A region (rs1023844, P\u2009=\u20099.6e\u221207) was also an eQTL and associated with BCG-induced monocyte PDL1 expression. In summary, we identified genetic variants associated with heterogeneity in infant BCG-induced innate immune responses with potential immunoregulatory mechanisms.<\/jats:p>","DOI":"10.1093\/jimmun\/vkae062","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T02:29:15Z","timestamp":1743647355000},"page":"936-946","source":"Crossref","is-referenced-by-count":2,"title":["BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-5554","authenticated-orcid":false,"given":"Christine","family":"Anterasian","sequence":"first","affiliation":[{"name":"University of Washington School of Medicine , Seattle, WA,","place":["United 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