Table 4.
Pleiotropy in terms of gene expression in relevant tissues, protein expression, diseases and effect on transcript for variants that showed novel associations with plasma protein and IgG N-glycosylation; the most biologically plausible candidates for observed novel associations are the C3 gene due to an associated missense variant located in the coding region and the associated Man9 glycan attached to its protein product surface, and the N-glycosyltransferase gene MGAT3
| Glycan | Glycan structure | Locus | Gene | SNP | Number of SNPs in the interval | Effect on transcript | eQTL in relevant tissues/tissue | pQTL; protein; tissue | Disease gene (s); disease |
|---|---|---|---|---|---|---|---|---|---|
| GP19 | Man9 | 19: 6,710,782–6,713,262 | C3 | rs1047286 | 2 |
Direct: rs1047286 missense coding variant, C3 protein pPro314Leu substitution Putative: C3 rs2230203 synonymous coding variant |
C8; C8; plasma | C3, C8A/B/G; increased risk of type 1 diabetes among HLA-DR4/4 carriers [41]a, macular degeneration, complement component 3 deficiency, haemolytic uraemic syndrome, complement component 8 deficiency type I/II | |
| IGP24 | FA2BG2S2 | 22: 39,843,409–39,844,793 | rs5757680 | 2 | Intergenic region | MGAT3/whole blood | IL6ST (sGP130); IL-6 receptor subunit β (gp130, soluble); plasma | IL6ST; hyper-IgE recurrent infection syndrome 4b | |
| IGP15 | FA2BG2 | 22: 39,739,638–39,756,985 | SYNGR1 | rs137702 | 7 | Putative: SYNGR1 intron variants (rs137702, rs137707, rs2413589, rs4821887) | MGAT3/B cells | IL6ST (sGP130); IL-6 receptor subunit β (gp130, soluble); plasma | IL6ST; hyper-IgE recurrent infection syndrome 4b |
Each locus is represented by the SNP with the strongest association in the region. Locus information is presented as ‘chromosome number: locus start – locus end’. The results are reported for GRCh Build 37. eQTL, pQTL, disease gene/disease, effect on transcript and LD were obtained using SNiPA [35], and SNPs were grouped in the same genomic interval based on LD (R2>0.5) with the top associated SNP within the interval
ars2230199 was previously associated with an increased risk of type 1 diabetes among HLA-DR4/4 carriers (R2=0.82 with rs1047286; R2=0.7 with rs2230203)
C8A/B/G, complement C8 α/β/γ chain gene; IL6ST, interleukin 6 cytokine family signal transducer gene; gp130, soluble glycoprotein 130 (synonyms: IL6ST, soluble)