Abstract
Genome-wide association studies (GWAS) have identified over 60 genetic loci associated with immunoglobulin G (IgG) N-glycosylation; however, the causal genes and their abundance in relevant tissues are uncertain. Leveraging data from GWAS summary statistics for 8,090 Europeans, and large-scale expression quantitative trait loci (eQTL) data from the genotype-tissue expression of 53 types of tissues (GTEx v7), we derived a linkage disequilibrium score for the specific expression of genes (LDSC-SEG) and conducted a transcriptome-wide association study (TWAS). We identified 55 gene associations whose predicted levels of expression were significantly associated with IgG N-glycosylation in 14 tissues. Three working scenarios, i.e., tissue-specific, pleiotropic, and coassociated, were observed for candidate genetic predisposition affecting IgG N-glycosylation traits. Furthermore, pathway enrichment showed several IgG N-glycosylation-related pathways, such as asparagine N-linked glycosylation, N-glycan biosynthesis and transport to the Golgi and subsequent modification. Through phenome-wide association studies (PheWAS), most genetic variants underlying TWAS hits were found to be correlated with health measures (height, waist-hip ratio, systolic blood pressure) and diseases, such as systemic lupus erythematosus, inflammatory bowel disease, and Parkinson’s disease, which are related to IgG N-glycosylation. Our study provides an atlas of genetic regulatory loci and their target genes within functionally relevant tissues, for further studies on the mechanisms of IgG N-glycosylation and its related diseases.
RAS ID
42679
Document Type
Journal Article
Date of Publication
2021
Funding Information
Edith Cowan University - Open Access Support Scheme 2021
Australia-China International Collaborative grant
National Health and Medical Research Council
National Natural Science Foundation of China
China Scholarship Council
Bioyong Industry Engagement Scholarship
Edith Cowan University
School
School of Medical and Health Sciences / Centre for Precision Health
Grant Number
NHMRC Number : APP1112767
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Publisher
Frontiers Media S.A.
Recommended Citation
Li, X., Wang, H., Zhu, Y., Cao, W., Manshu, S., Wang, Y., Hou, H., Lang, M., Guo, X., Tan, X., Han, J. J., & Wang, W. (2021). Heritability enrichment of immunoglobulin G N-glycosylation in specific tissues. DOI: https://doi.org/10.3389/fimmu.2021.741705
Comments
Li, X., Wang, H., Zhu, Y., Cao, W., Song, M., Wang, Y., . . . Wang, W. (2021). Heritability enrichment of immunoglobulin G N-glycosylation in specific tissues. Frontiers in Immunology, 12, article 741705. https://doi.org/10.3389/fimmu.2021.741705