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TCF3-PBX1 fusion defines a common molecular subtype of ALL with unique clinical features, but the molecular basis of its inherited susceptibility is unknown. In a genome-wide association study of 1494 ALL cases and 2057 non-ALL controls, we identified a germline risk locus located in an intergenic region between BCL11A and PAPOLG: rs2665658, P\u2009=\u20091.88\u2009\u00d7\u200910\u20138 for TCF3-PBX1 ALL vs non-ALL, and P\u2009=\u20091.70\u2009\u00d7\u200910\u20138 for TCF3-PBX1 ALL vs other-ALL. The lead variant was validated in a replication cohort, and conditional analyses pointed to a single causal variant with subtype-specific effect. The risk variant is located in a regulatory DNA element uniquely activated in ALL cells with the TCF3-PBX1 fusion and may distally modulate the transcription of the adjacent gene REL. Our results expand the understanding of subtype-specific ALL susceptibility and highlight plausible interplay between germline variants and somatic genomic abnormalities in ALL pathogenesis.<\/jats:p>","DOI":"10.1093\/jnci\/djaa133","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T11:10:00Z","timestamp":1598440200000},"page":"933-937","source":"Crossref","is-referenced-by-count":13,"title":["Genome-Wide Association Study of Susceptibility Loci for <i>TCF3-PBX1<\/i> Acute Lymphoblastic Leukemia in Children"],"prefix":"10.1093","volume":"113","author":[{"given":"Shawn\u00a0H. 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