rs10764775 (LINC01163): IgG Glycosylation Variant

Key takeaways

• rs10764775, near the LINC01163 and LINC02667 long non-coding RNA (lncRNA) genes, was found in a genome-wide study of IgG antibody sugar-chain (N-glycan) patterns measured in over 4,000 Europeans.
• The locus overlaps with genomic regions previously associated with autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes.
• The same region is also connected to blood cancers such as Hodgkin lymphoma and acute lymphoblastic leukaemia.
• The alternative allele at this variant is linked to reduced expression of a nearby lncRNA gene in non-sun-exposed skin, based on large-scale tissue expression data.

What the research says A genome-wide association study (GWAS) of immunoglobulin G (IgG) N-glycosylation, the process by which sugar chains are attached to IgG antibodies and shape their immune function, measured 77 distinct glycan traits using ultra-performance liquid chromatography (UPLC) in 2,247 Europeans, with replication in 1,848 Europeans. Nine loci reached genome-wide significance (P<2.27x10^-9), and the authors note that loci not directly encoding glycosylation enzymes showed strong overlap with autoimmune and inflammatory diseases and haematological (blood) cancers, a pattern relevant to this locus. Tissue-specific expression data from GTEx v11 (953 donors) shows that the alternative allele at rs10764775 is associated with reduced expression of ENSG00000300601 in non-sun-exposed suprapubic skin (slope -0.15, p=2.1e-5) GTEx Portal.

Reported associations

• IgG N-glycosylation: Linked to 77 measured sugar-chain traits on IgG antibodies in a GWAS of 2,247 European discovery samples, with replication in 1,848, at a genome-wide significance threshold of P<2.27x10^-9.
• Autoimmune disease pleiotropy: The locus overlaps with regions associated with systemic lupus erythematosus (SLE), rheumatoid arthritis, ulcerative colitis, Crohn's disease, type 1 diabetes, multiple sclerosis, Graves' disease, celiac disease, and nodular sclerosis.
• Haematological cancer associations: The locus shows pleiotropic overlap with regions associated with acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma.
• Skin cis-eQTL: The alternative allele is associated with reduced expression of ENSG00000300601 in non-sun-exposed suprapubic skin GTEx Portal.

Evidence quality The primary GWAS measured 77 IgG glycan traits in 2,247 Europeans across four discovery cohorts and replicated findings in 1,848 Europeans, with genome-wide significance set at P<2.27x10^-9 to account for multiple testing across glycan traits. Replication was specifically confirmed for two loci (B4GALT1 and MGAT3); the replication status of rs10764775 is not explicitly described in the available study text, and the association at this locus should therefore be treated as preliminary. The pleiotropic connections to autoimmune and haematological conditions are noted in the study as observed genomic overlaps across related loci, not established causal relationships at this specific variant. The GTEx cis-eQTL effect in skin (slope -0.15, p=2.1e-5) is modest, confined to a single tissue type, and may suggest a molecular mechanism but does not independently establish clinical significance.

Tissue-specific expression effects

• ENSG00000300601 (lncRNA at this locus): Reduced expression in non-sun-exposed suprapubic skin. No other tissues showed a significant cis-eQTL effect at FDR<0.05 in the provided GTEx v11 data GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.