Abstract
Most human proteins are glycosylated. Attachment of complex oligosaccharides to the polypeptide part of these proteins is an integral part of their structure and function and plays a central role in many complex disorders. One approach towards deciphering this human glycan code is to study natural variation in experimentally well characterized samples and cohorts. High-throughput capable large-scale methods that allow for the comprehensive determination of blood circulating proteins and their glycans have been recently developed, but so far, no study has investigated the link between both traits. Here we map for the first time the blood plasma proteome to its matching N-glycome by correlating the levels of 1116 blood circulating proteins with 113 N-glycan traits, determined in 344 samples from individuals of Arab, South-Asian, and Filipino descent, and then replicate our findings in 46 subjects of European ancestry. We report protein-specific N-glycosylation patterns, including a correlation of core fucosylated structures with immunoglobulin G (IgG) levels, and of trisialylated, trigalactosylated, and triantennary structures with heparin cofactor 2 (SERPIND2). Our study reveals a detailed picture of protein N-glycosylation and suggests new avenues for the investigation of its role and function in the associated complex disorders.
Highlights
Protein glycosylation is a ubiquitous form of protein modification and plays a central role in many biological processes [1]
We found excellent agreement between both studies: of the 23 strongest C-reactive protein (CRP)-glycan associations observed in TwinsUK, only one was not significant (p < 3.96 × 10−7 ) in Qatar Metabolomics Study on Diabetes (QMDiab), while only four out of the 90 remaining weaker association were replicated in QMDiab
Targeted mass-spectrometry methods can for instance be deployed to confirm and glycans and proteins
Summary
Protein glycosylation is a ubiquitous form of protein modification and plays a central role in many biological processes [1]. Carbohydrates are one of the major biological building blocks, understanding of the human glycan code lags far behind that of DNA, RNA, and proteins. Metabolites 2019, 9, 122 interface [4], the link between the blood methylome and metabolome [5], and genome-wide association studies with the blood proteome [6] and metabolome [7]. We extend this approach to investigate the relationship between natural variation observed in the blood circulating proteome and its associated
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