rs11697848 (KRT18P4): Lupus GWAS & Brain eQTL
Key takeaways
- rs11697848 near KRT18P4 and RNU6-147P was identified in a genome-wide lupus study using a false discovery rate significance threshold
- The variant is associated with reduced SPATA2 expression in the cerebellum, cerebellar hemisphere, caudate basal ganglia, and pituitary gland
- The SLE genetic association is preliminary; independent replication at this locus is not yet reported
- GTEx data from 953 donors show the brain expression signal reaches p = 5.3×10^-9 in cerebellar tissue, indicating a well-powered expression effect
Key takeaways
- rs11697848 near KRT18P4 and RNU6-147P was identified in a genome-wide lupus study using a false discovery rate significance threshold
- The variant is associated with reduced SPATA2 expression in the cerebellum, cerebellar hemisphere, caudate basal ganglia, and pituitary gland
- The SLE genetic association is preliminary; independent replication at this locus is not yet reported
- GTEx data from 953 donors show the brain expression signal reaches p = 5.3×10^-9 in cerebellar tissue, indicating a well-powered expression effect
What the research says A genome-wide association study (GWAS) of systemic lupus erythematosus (SLE - an autoimmune disease in which the immune system attacks the body's own tissues) in individuals of European ancestry applied imputation, stepwise multiple regression, and lasso regularization (a statistical technique that removes redundant signals), using a false discovery rate (FDR) threshold of ≤0.05 rather than the stricter Bonferroni correction; across non-HLA genomic regions (all chromosomal areas outside the major immune-gene cluster), the study detected 25 significant single nucleotide polymorphisms (SNPs - single-letter DNA variants) across 17 genes, including 13 previously unreported SLE associations. Separately, tissue-specific gene-expression data from GTEx version 11 (953 donors, cis-window analysis) show that the alternate allele of rs11697848 is associated with reduced SPATA2 expression across four tissues, with the strongest reduction in cerebellar cortex GTEx Portal.
Reported associations
- Systemic lupus erythematosus: rs11697848, situated near the KRT18P4 (a non-functional pseudogene copy of the keratin 18 gene) and RNU6-147P (a U6 small nuclear RNA pseudogene) loci, was captured among 25 non-HLA significant SNPs in an SLE GWAS of European-ancestry individuals using FDR ≤0.05 significance; no effect size specific to this SNP is stated in the provided text
- SPATA2 expression - brain and pituitary eQTL: The alternate allele is associated with reduced SPATA2 expression in cerebellar cortex (slope −0.55, p = 5.3×10^-9), cerebellar hemisphere (slope −0.47, p = 2.2×10^-7), pituitary gland (slope −0.32, p = 3.7×10^-5), and caudate basal ganglia (slope −0.30, p = 7.3×10^-5) - a consistent directional pattern across four independent tissues GTEx Portal
Evidence quality The SLE association derives from a single GWAS that deliberately chose FDR over family-wise error rate (FWER) correction to increase statistical power; the study explicitly acknowledges this trade-off and notes that only 4 of its 13 novel gene regions met the stricter FWER threshold while others did not. Overall study sample size is not specified in the provided text, and independent replication of this specific locus is not described - placing the SLE signal in the preliminary category. The eQTL evidence from GTEx is better supported: 953 donors, consistent reduction in SPATA2 expression across four anatomically distinct tissues, and p-values ranging from 7.3×10^-5 in the caudate to 5.3×10^-9 in the cerebellum, all comfortably below standard eQTL significance thresholds GTEx Portal. No conflicting findings are present in the provided studies.
Tissue-specific expression effects
- SPATA2: The alternate allele is associated with reduced expression across four tissues - most strongly in the cerebellum, followed by the cerebellar hemisphere, pituitary gland, and caudate basal ganglia; the effect is directionally consistent (reduced in all four) GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs11697848 associated with?
rs11697848 was flagged in a genome-wide association study of systemic lupus erythematosus (an autoimmune disease). Separately, GTEx expression data link it to reduced SPATA2 gene activity in the cerebellum, cerebellar hemisphere, caudate basal ganglia, and pituitary gland.
What are KRT18P4 and RNU6-147P?
KRT18P4 is a pseudogene, meaning a non-functional DNA copy of the keratin 18 gene. RNU6-147P is a pseudogene of U6 small nuclear RNA. rs11697848 sits in the genomic region near both of these non-coding elements.
How strong is the evidence linking rs11697848 to lupus?
The association comes from a single genome-wide study that used a false discovery rate threshold rather than the stricter Bonferroni correction. Independent replication of this specific locus is not described in the available literature, so the lupus link should be considered preliminary.
What does GTEx data show for rs11697848?
GTEx version 11 data from 953 donors show that carriers of the alternate allele tend to have lower SPATA2 gene expression in four tissues: cerebellum, cerebellar hemisphere, caudate basal ganglia, and pituitary gland. The strongest signal is in cerebellar tissue at p = 5.3×10^-9.
Is rs11697848 linked to any brain conditions?
The provided studies do not associate rs11697848 with any specific brain condition. The GTEx data show it affects SPATA2 expression levels in brain regions, but an expression effect (eQTL) is not the same as an established disease association.