Novel loci associated with plasma immunoglobulin G N-glycosylation identified by a multivariate analysis

Poster (download) Video (download) Alexandra S. Shadrina1, Alexander S. Zlobin2, Olga O. Zaytseva3, Gordan Lauc4, Lucija Klaric5, Sodbo Z. Sharapov6, Yurii S. Aulchenko7, Yakov A. Tsepilov81Laboratory of Glycogenomics, Institute of Cytology and Genetics, Novosibirsk, Russia, weiner.alexserg@gmail.com2Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Novosibirsk, Russia, defrag12@gmail.com3Genos Glycoscience Research Laboratory, Zagreb, Croatia, lomur00@gmail.com4Genos Glycoscience Research Laboratory, Zagreb, Croatia, glauc@genos.hr5MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom, Lucija.Klaric@ed.ac.uk6Laboratory of Glycogenomics, Institute of Cytology and Genetics, Novosibirsk, Russia, sharapovsodbo@gmail.com7Laboratory of Glycogenomics, Institute of Cytology and Genetics, Novosibirsk, Russia, y.s.aulchenko@polyomica.com8Laboratory of Theoretical and Applied Functional Genomics, Novosibirsk State University, Novosibirsk, Russia, drosophila.simulans@gmail.com Immunoglobulin G (IgG) is the most prevalent human plasma N-glycosylated protein, which makes a significant impact into the total plasma protein glycosylation profile. Glycosylation of IgG is known to affect its biological properties; for example, sialylation of glycans attached to IgG is known to have an anti-inflammatory effect, while the absence of a core fucose in the IgG glycan structure can increase antigen-dependent cell cytotoxicity. The biochemical processes underlying protein glycosylation are well-studied; at the same time, little is known about biological network regulating these reactions. In the present study, we performed a multivariate analysis based on the summary statistics obtained in the previously published IgG N-glycome GWAS in order to discover new loci influencing IgG N-glycosylation patterns. We revealed thirty-four loci associated with the levels of plasma IgG N-glycosylation. Of these loci, eight loci have not been reported in previous works. Our results significantly expand the number of identified IgG N-glycome-associated loci and contribute to understanding the mechanisms of the genetic control of glycosylation.

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