rs111508444 (GABBR1-SUMO2P1): eQTL across 8 tissues
Key takeaways
- rs111508444 lies between GABBR1 (a major inhibitory GABA receptor gene) and SUMO2P1 (a pseudogene), a region with roles in both nerve signaling and protein modification.
- The alternate allele reduces nearby gene expression in 8 tissues including whole blood, spleen, and both visceral and subcutaneous fat.
- A large lumbar disc herniation GWAS (80,724 cases, 748,975 controls) found novel loci near synaptic transmission genes, the pathway that includes GABBR1.
- Disease-association evidence for this specific variant is preliminary; eQTL expression effects are the strongest documented finding.
Key takeaways
- rs111508444 lies between GABBR1 (a major inhibitory GABA receptor gene) and SUMO2P1 (a pseudogene), a region with roles in both nerve signaling and protein modification.
- The alternate allele reduces nearby gene expression in 8 tissues including whole blood, spleen, and both visceral and subcutaneous fat.
- A large lumbar disc herniation GWAS (80,724 cases, 748,975 controls) found novel loci near synaptic transmission genes, the pathway that includes GABBR1.
- Disease-association evidence for this specific variant is preliminary; eQTL expression effects are the strongest documented finding.
What the research says GTEx v11 (Genotype-Tissue Expression project, 953 donors, false discovery rate < 0.05) identifies rs111508444 as an eQTL - a variant influencing how much a nearby gene is expressed - for ENSG00000285761, with the alternate allele reducing expression most strongly in spleen (slope −0.73) and consistently across 7 additional tissues GTEx Portal. A genome-wide meta-analysis of lumbar disc herniation (LDH) across FinnGen, the Estonian Biobank, and UK Biobank (80,724 cases, 748,975 controls) identified 64 genome-wide significant loci - 41 previously unreported - including candidates near synaptic transmission genes; GABBR1 encodes the primary inhibitory gamma-aminobutyric acid type B (GABA-B) receptor and belongs to this functional category. Large East Asian GWAS efforts have additionally surveyed this chromosomal region for systemic lupus erythematosus (SLE; 208,370 individuals, 113 loci identified) and for cross-trait associations between Hunner-type interstitial cystitis (HIC) and autoimmune diseases (~170,000 individuals, 64 pleiotropic SNPs identified).
Reported associations
- Gene expression (eQTL, ENSG00000285761): The alternate allele is associated with reduced expression in spleen, visceral adipose (omentum), subcutaneous adipose, EBV-transformed lymphocytes, esophageal gastroesophageal junction, transverse colon, whole blood, and lung; log2-normalized effect sizes range from −0.51 in lung to −0.73 in spleen GTEx Portal
- Lumbar disc herniation (synaptic pathway context): A three-biobank meta-analysis (80,724 cases, 748,975 controls) catalogued novel genome-wide significant loci near synaptic transmission genes; the locus encodes GABBR1, a canonical inhibitory GABA-B receptor placing it in this candidate gene category
Evidence quality The strongest evidence for this locus is the multi-tissue eQTL: GTEx v11 data from 953 donors shows the alternate allele reduces ENSG00000285761 expression in 8 independent tissues at FDR < 0.05, with effect sizes ranging from −0.51 in lung to −0.73 in spleen and no directional conflicts across tissues GTEx Portal. Disease-association evidence is more indirect. The LDH meta-analysis is large and well-powered (80,724 cases, genome-wide significance p < 5×10^-8) and explicitly names synaptic transmission as a novel candidate pathway, but the available text does not individually name rs111508444 as a confirmed signal; that connection is provisional. The SLE meta-analysis (208,370 East Asians; 113 significant regions; conditional analysis detecting 233 signals; Bayesian fine-mapping prioritising causal variants in 28 loci to credible sets of 10 or fewer) and the HIC cross-trait study (64 independent pleiotropic SNPs from ~170,000 East Asians) are large and methodologically rigorous but do not explicitly document an association at this variant in the available excerpts. No conflicting findings are present among the available data, and independent replication of any disease association at rs111508444 is not reported in the provided studies.
Tissue-specific expression effects
- ENSG00000285761: The alternate allele is associated with reduced expression in spleen (largest effect), visceral adipose (omentum), subcutaneous adipose, EBV-transformed lymphocytes, esophageal gastroesophageal junction, transverse colon, whole blood, and lung GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is the GABBR1 gene?
GABBR1 encodes the gamma-aminobutyric acid type B receptor subunit 1, a component of GABA-B receptors that mediate inhibitory signals in the brain and nervous system. These receptors regulate neural excitability and are involved in pain processing and neurological function.
What does rs111508444 do to gene expression?
GTEx data from 953 donors shows the alternate allele at rs111508444 is associated with reduced expression of a nearby gene (ENSG00000285761) in 8 tissues including whole blood, spleen, adipose, and lung. This type of regulatory influence on nearby gene expression is called an eQTL.
Is rs111508444 linked to lumbar disc herniation?
A large GWAS meta-analysis of lumbar disc herniation identified novel risk loci near synaptic transmission genes, and GABBR1 belongs to that functional category. The available evidence does not explicitly confirm an independent signal at rs111508444 itself; the connection is considered contextual and preliminary.
What is SUMO2P1?
SUMO2P1 is a pseudogene related to SUMO2, which encodes a small ubiquitin-like modifier protein involved in regulating protein activity inside cells. Some pseudogenes can influence the regulation of neighboring genes in their genomic region.
Which tissues show the rs111508444 eQTL effect?
GTEx v11 data shows reduced expression of ENSG00000285761 in spleen, visceral adipose, subcutaneous adipose, EBV-transformed lymphocytes, esophagus, transverse colon, whole blood, and lung. The largest effect is in spleen and the smallest is in lung.