Citrus huanglongbing (HLB), or greening, is the most destructive citrus disease worldwide, and threatens the sustainability of the industry, affecting tree development, production, and fruit quality. All Asian citrus species, including all commercial varieties, are susceptible to HLB; however, tolerance and resistance have been described in some citrus relatives belonging to the Oceanian genera Microcitrus and Eremocitrus. Species of these genera are sexually compatible with Citrus spp.. CIRAD has generated a unique diversity panel of diploid intergeneric-hybrids (Citrus sp. x Microcitrus sp.) over several generations. FUNDECITRUS, whilst, has generated several biparental populations of intergeneric-hybrids (Citrus sp. x Microcitrus sp.) from first and second generation issued from controlled crosses. Such wide crosses may result in non-Mendelian inheritance of phenotypic traits due to the reformatting of the epigenetic landscape. The overall objective of the EpiHLB project is to identify genes and genomic regions associated with HLB resistance and to determine how their expression is controlled. A core collection of intergeneric-hybrids will be selected from the CIRAD and FUNDECITRUS populations, and their response to infection will be studied under HLB challenge inoculation stress. The project will focus on the role of genetic and epigenetic factors in the regulation of gene expression linked to HLB resistance by developing a multi-omic quantitative approach that combines multiple layers of association studies. The strategy is to join genomic (GBS and WGS), transcriptomic (RNA-seq and small RNAseq), and epigenetic (methylome) studies to the phenotype in order to develop models of omics-association. In the framework of the implementation of sustainable integrated pest management, the results of this project will contribute to the development of innovative strategies to create cultivars and rootstocks resistant to this disease, severely affecting a socioeconomically important crop worldwide.