Glycosylation is one of the most extensive protein modifications. Glycans influence both structure and function of the proteins and known to have important roles in physiological and pathological processes. The absence of a universal code for glycan synthesis combined with the technological challenges faced by glycan quantification analysis has hindered the knowledge about the processes regulating the assembly of glycans. Major breakthroughs in analytical procedures created the possibility to reliably quantify glycans in a high-throughput manner and allowed the first large-scale studies on human plasma N-glycome. In order to explore the genomic and environmental regulation of glycosylation, different computational methods were employed to the integrated analysis of glycan, physiological/biochemical and genotype data in three isolated population cohorts. Specific glyco-phenotypes were identified in the general population and the potential use of glycan modifications as biomarkers was evaluated for the particular case of diabetes. General associations between glycans and phenotypes were observed and glycan, phenotypic and genotypic patterns capable of discriminating the populations were explored. The analysis of polymorphisms associated with glycosylation was addressed replicating previous findings and suggesting possible novel associations.