engleski

Genome-wide association meta-analysis of IgG N- glycan traits measured with different quantification platforms

Goal: Glycosylation of Fc binding region of immunoglobulin G (IgG) is a highly complex biosynthetic pathway which involves large network of genes, thus making our understanding of it very limited. Previous genome-wide associations scans (GWAS) of IgG glycan traits included IgG glycan samples quantified either by UPLC (Ultra performance liquid chromatography) or LCMS (Liquid chromatography coupled with mass spectrometry) platform. We conducted a pilot genome-wide association meta analysis, including both LCMS and UPLC measured IgG glycan samples, aiming to increase power to identify novel genetic variants associated to IgG glycosylation pathway. Materials and methods: GWAS were performed in four cohorts of European descent (CROATIA-Korcula, CROATIA-Vis, CROATIA-Split, ORCADES) with total sample size of 6, 036. Glycan traits were defined as percentage of presence of sugar moiety in the total IgG N-glycome. Association between glycan traits and HRC imputed genetic data was performed using additive linear model as a model of association. Meta analysis on summary statistics of the four cohorts was performed with METAL software using fixed effect inverse- variance meta-analysis method. Results: In our pilot study, we uncovered fourteen genome-wide significant loci which were identified in previous IgG glycosylation GWAS, including glycosyltransferease genes (FUT8, B4GALT1, ST6GAL and MGAT3), as well as genes encoding for transcription factors, transporters and chromatin remodelling proteins. Conclusion: This strategy allowed us to retrieve loci previously associated to IgG glycosylation, suggesting that this approach of platform harmonisation is suitable for genetic association studies. This will enable us to increase the total sample size in the meta analysis by including additional cohorts and thereby maximizing the power to detect novel loci having a role in IgG glycosylation pathway.

IgG ; glycosylation ; GWAS

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