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In a context of fertiliser reduction, breeding for enhanced nitrogen use efficiency in bread wheat is necessary. This PhD thesis resulting from private-public collaboration between the French National Institute for Agricultural Research and Biogemma aimed providing necessary tools. Analyses were conducted using a dataset of 225 commercial varieties genotyped with 24K SNP and tested in eight combinations of year, location, and nitrogen regimes. We showed that even if past selection increased nitrogen use efficiency at high and moderate nitrogen regimes, genetic progresses need to be accelerated and better balanced between traits. This could be achieved by mixing phenotypic and marker assisted selections. In this sense, we developed a method to define quantitative trait locus from genome-wide association study: 333 chromosomal regions involved in 28 NUE-related traits have been identified. The NAM-A1 gene was located in one of these regions and its natural variants were characterized. We also showed that genomic selection could be improved by pre-selecting SNP based on their significance in a multi-environmental genome-wide association study. Networks of epistasis interactions were also studied and an interesting sub-network was identified. Results and methods are discussed regarding breeding and gene discovery strategy. Further investigations and improvements are suggested.