25Plant disease resistance is largely governed by complex genetic architecture. In maize, few 26 disease resistance loci have been characterized. Near-isogenic lines (NILs) are a powerful 27 genetic tool to dissect quantitative trait loci (QTL). We analyzed an introgression library of 28 maize near-isogenic lines (NILs), termed a nested NIL (nNIL) library for resistance to northern 29 leaf blight (NLB) caused by the fungal pathogen Setosphaeria turcica. The nNIL library was 30 comprised of 412 BC5F4 NILs that originated from 18 diverse donor parents and a common 31 recurrent parent, B73. Single nucleotide polymorphisms identified through genotyping by 32 sequencing (GBS) were used to define introgressions and for association analysis. NILs that 33 conferred resistance and susceptibility to NLB were comprised of introgressions that overlapped 34 known NLB QTL. Genome-wide association analysis and stepwise regression further resolved 35 five QTL regions, and implicated several candidate genes, including Liguleless1 (Lg1), a key 36 determinant of leaf architecture in cereals. Two independently-derived mutant alleles of lg1 37 inoculated with S. turcica showed enhanced susceptibility to NLB. In the maize nested 38 association mapping population, leaf angle was positively correlated with NLB in five 39 recombinant inbred line (RIL) populations, and negatively correlated with NLB in four RIL 40 populations. This study demonstrates the power of a nNIL library combined with high density 41 SNP coverage to resolve QTLs. Furthermore, the role of lg1 in leaf architecture and in resistance 42 to NLB has important applications in crop improvement.43 44Significance Statement (120 words) 45 Understanding the genetic basis of disease resistance is important for crop improvement. We 46 analyzed response to northern leaf blight (NLB) in a maize population consisting of 412 near-47 isogenic lines (NILs) derived from 18 diverse donor parents backcrossed to a recurrent parent, 48 B73. NILs were genotyped by sequencing to detect introgressed segments. We identified NILs 49 with greater resistance or susceptibility to NLB than B73. Genome-wide association analysis, 50 coupled with stepwise regression, identified 5 candidate loci for NLB resistance, including the 51 liguleless1 gene. The LIGULELESS1 transcription factor is critical in development of the leaf 52 ligular region and influences leaf angle. We found that liguleless1 mutants are significantly more 53 susceptible to NLB, uncovering a pleiotropic role for liguleless1 in development and disease 54 resistance. 55 56 57 58