Increased fasting plasma glucose (FPG) is an independent risk factor for type 2 diabetes mellitus (T2DM). The development of systems biology technologies for integration of multiomics data is crucial for predicting increased FPG levels. In this case-control study, immunoglobulin (Ig) G glycosylation profiling and genome-wide association analyses were performed on 511 participants, and among them 76 had increased FPG (aged 47.6 ± 6.14 years), and 435 had decreased or fluctuant FPG (aged 47.9 ± 6.08 years). We identified nine single nucleotide polymorphisms (SNPs) in five genes (RPL7AP27, SNX30, SLC39A12, BACE2, and IGFL2) that were significantly associated with increased FPG (odds ratios 1.937-2.393). Moreover, of the 24 glycan peaks (GPs), GPs 3, 8, and 11 presented positive trends with increased FPG levels, whereas GPs 4 and 14 presented negative trends. A significant improvement of predictive power was observed when adding 24 IgG GPs to 9 SNPs with the area under the curve increased from 0.75 to 0.81. This report shows that the combination of candidate SNPs with IgG glycomics offers biomarker potentials for T2DM. The substantial predictive power obtained from integrating genomics and glycomics biomarkers suggests the feasibility of applying such multiomics strategies to enable predictive, preventive, and personalized medicine for T2DM.
Keywords: IgG glycosylation; T2DM; biomarker discovery; genome-wide association study; multiomics; predictive models.