The genetics and epidemiology of N- and O-immunoglobulin A glycomics.
Autor: | Visconti A; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.; Center for Biostatistics, Epidemiology and Public Health, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy., Rossi N; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Bondt A; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Ederveen AH; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Thareja G; Department of Biophysics and Physiology, Weill Cornell Medicine-Qatar, Doha, Qatar., Koeleman CAM; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Stephan N; Department of Biophysics and Physiology, Weill Cornell Medicine-Qatar, Doha, Qatar., Halama A; Department of Biophysics and Physiology, Weill Cornell Medicine-Qatar, Doha, Qatar., Lomax-Browne HJ; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, UK., Pickering MC; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, UK., Zhou XJ; Renal Division, Peking University First Hospital, Beijing, China.; Peking University Institute of Nephrology, Beijing, China.; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Peking University, Beijing, China., Wuhrer M; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Suhre K; Department of Biophysics and Physiology, Weill Cornell Medicine-Qatar, Doha, Qatar., Falchi M; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. mario.falchi@kcl.ac.uk. |
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Jazyk: | angličtina |
Zdroj: | Genome medicine [Genome Med] 2024 Aug 09; Vol. 16 (1), pp. 96. Date of Electronic Publication: 2024 Aug 09. |
DOI: | 10.1186/s13073-024-01369-6 |
Abstrakt: | Background: Immunoglobulin (Ig) glycosylation modulates the immune response and plays a critical role in ageing and diseases. Studies have mainly focused on IgG glycosylation, and little is known about the genetics and epidemiology of IgA glycosylation. Methods: We generated, using a novel liquid chromatography-mass spectrometry method, the first large-scale IgA glycomics dataset in serum from 2423 twins, encompassing 71 N- and O-glycan species. Results: We showed that, despite the lack of a direct genetic template, glycosylation is highly heritable, and that glycopeptide structures are sex-specific, and undergo substantial changes with ageing. We observe extensive correlations between the IgA and IgG glycomes, and, exploiting the twin design, show that they are predominantly influenced by shared genetic factors. A genome-wide association study identified eight loci associated with both the IgA and IgG glycomes (ST6GAL1, ELL2, B4GALT1, ABCF2, TMEM121, SLC38A10, SMARCB1, and MGAT3) and two novel loci specifically modulating IgA O-glycosylation (C1GALT1 and ST3GAL1). Validation of our findings in an independent cohort of 320 individuals from Qatar showed that the underlying genetic architecture is conserved across ancestries. Conclusions: Our study delineates the genetic landscape of IgA glycosylation and provides novel potential functional links with the aetiology of complex immune diseases, including genetic factors involved in IgA nephropathy risk. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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