Fusarium crown rot (FCR) is one of the most important diseases of wheat (Triticum aestivum L.). fcRis mainly caused by the fungal pathogens Fusarium culmorum and F. pseudograminearum. In order to identify new sources of resistance to FCR and to dissect the complexity of FCR resistance, a panel of 161 wheat accessions was phenotyped under growth room (GR) and greenhouse conditions (GH). Analysis of variance showed significant differences in crown rot development among wheat accessions and high heritability of genotype-environment interactions for GR (0.96) and GH (0.91). Mixed linear model analysis revealed seven novel quantitative trait loci (QTLs) linked to F. culmorum on chromosomes 2AL, 3AS, 4BS, 5BS, 5DS, 5DL and 6DS for GR and eight QTLs on chromosomes on 3AS, 3BS, 3DL, 4BS (2), 5BS, 6BS and 6BL for GH. Total phenotypic variances (R²) explained by the QTLs linked to GR and GH were 48% and 59%, respectively. In addition, five favorable epistasis interactions among the QTLs were detected for both GR and GH with and without main effects. Epistatic interaction contributed additional variation up to 21% under GR and 7% under GH indicating strong effects of environment on the expression of QTLs. Our results revealed FCR resistance responses in wheat to be complex and controlled by multiple QTLs.www.nature.com/scientificreports www.nature.com/scientificreports/ of inheritance, and strong genotype-by-environment interaction 20-23 . Further, molecular mechanisms of FCR resistance and interaction with environment are poorly understood. Thus, characterizing potential epistatic interactions between QTLs and environment will provide new insight in understanding the genetic basis of FCR resistance.Wheat accessions of different origin comprise a broad genetic diversity which can be exploited to breed for high yielding and disease resistant cultivars. Current progress in high density mapping, sequence availability and statistical tools make it possible to uncover the majority of QTL effects and functionally characterize their role in host-pathogen interactions. Genome-wide association study (GWAS) is a powerful approach to detect associations between phenotypic variation and genetic polymorphisms; in this way, QTLs for traits such as FCR can be located in the genome. GWAS utilizes linkage disequilibrium to dissect the genetic architecture of complex traits by correlating phenotypes to genotypes. It has been used earlier to identify QTLs that are involved in plant responses to soil borne pathogens in a large set of unrelated wheat accessions 19,24 . Detection of QTLs tightly linked to gene/s that control FCR resistance are the pre-requisite for marker assisted breeding. In the present study, we analyze the genetic basis of the FCR infection, disease development, and the interaction accross multiple environments. Our study not only confirmed previously described QTLs linked to FCR but also identified novel QTLs that have additive main and epistatic effects on FCR resistance which upon functional validation would provide addit...