Defining the genetic control of human blood plasma N-glycome using genome-wide association study

Glycosylationis a common post-translational modification of proteins. It is known, that glycans are directly involved in the pathophysiology of every major disease. Defining genetic factors altering glycosylationmay provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here, we report a genome-wide association studyof the human blood plasmaN- glycomecomposition in up to 3811 people. We discovered and replicated twelve loci. This allowed us to demonstrate a clear overlap in genetic control between total plasma and IgG glycosylation. Majority of loci contained genes that encode enzymes directly involved in glycosylation(FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3, and MGAT5). We, however, also found loci that are likely to reflect other, more complex, aspects of plasma glycosylation process. Functional genomicannotation suggested the role of DERL3, which potentially highlights the role of glycoprotein degradation pathway, and such transcription factor as IKZF1.