rs112259525 (GYG1P2): CSF sTREM2 and Alzheimer's
Key takeaways
- rs112259525 maps to a region containing two pseudogenes, GYG1P2 and RNU6-67P, with no protein-coding function
- The variant was flagged in a GWAS of cerebrospinal fluid soluble TREM2, an immune marker that rises with Alzheimer's disease stage
- Soluble TREM2 in spinal fluid correlates with tau protein levels, a hallmark Alzheimer's biomarker, across all disease stages
- Evidence is preliminary, based on a single cohort of 1,001 participants with no reported independent replication
Key takeaways
- rs112259525 maps to a region containing two pseudogenes, GYG1P2 and RNU6-67P, with no protein-coding function
- The variant was flagged in a genome-wide association study (GWAS) of cerebrospinal fluid (CSF) soluble TREM2, an immune marker that rises with Alzheimer's disease stage
- Soluble TREM2 in spinal fluid correlates with tau protein levels, a hallmark Alzheimer's biomarker, across all disease stages
- Evidence is preliminary, based on a single cohort of 1,001 participants with no reported independent replication
What the research says A GWAS of CSF soluble TREM2 (sTREM2) - a shed fragment of the TREM2 receptor on microglia (the brain's resident immune cells), measurable in spinal fluid - was conducted in 1,001 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), ranging from cognitively normal individuals through those with diagnosed Alzheimer's disease. rs112259525, at the GYG1P2 - RNU6-67P locus, was among the variants examined in this analysis; the study's most statistically significant reported hit was rs7232 in the MS4A6A gene on chromosome 11 (FDR = 3.01×10^-8). Across all disease states, CSF sTREM2 correlated positively with CSF total tau (ρ > 0.35, p < 1×10^-6) and phosphorylated-tau (ρ > 0.32, p < 1×10^-5), and sTREM2 levels rose with advancing disease stage.
Reported associations
- CSF soluble TREM2 (sTREM2) levels: rs112259525, in the GYG1P2 - RNU6-67P region, was identified as an associated variant in a GWAS of CSF sTREM2 among 1,001 ADNI participants spanning healthy controls to Alzheimer's disease; no specific effect size for this locus is provided in the available study text
- Alzheimer's disease neuroinflammation pathway: Pathway analysis of significant associations from the same GWAS found that biological processes for regulation of viruses and immune response were highly overrepresented, suggesting an immune and viral context for sTREM2 biology
Evidence quality The available evidence derives from a single GWAS (N = 1,001) using the ADNI cohort, a clinically heterogeneous sample spanning five diagnostic groups: healthy normal, significant memory concern, early mild cognitive impairment, late mild cognitive impairment, and Alzheimer's disease. No variant-specific p-value, false discovery rate, or effect size for rs112259525 is given in the supplied study text; the most significant association reported in the same study was rs7232 (FDR = 3.01×10^-8). The study is not accompanied by a PubMed identifier in the provided metadata, which limits direct citation verification. No independent replication of this locus is described in the provided literature. Overall, evidence for rs112259525 should be regarded as preliminary.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What genes are near rs112259525?
rs112259525 sits in a region containing GYG1P2 and RNU6-67P, both pseudogenes - non-functional genomic sequences resembling the glycogenin-1 gene and a small nuclear RNA gene respectively. Neither encodes a working protein.
What trait is rs112259525 associated with?
It has been investigated in relation to cerebrospinal fluid levels of soluble TREM2, a protein fragment released by the TREM2 immune receptor on microglia, the brain's immune cells. Elevated soluble TREM2 in spinal fluid is considered a marker of neuroinflammation in Alzheimer's disease research.
What is soluble TREM2 and why does it matter in Alzheimer's disease research?
Soluble TREM2 is a fragment of the TREM2 receptor shed by microglia and detectable in cerebrospinal fluid. Research has found that its levels rise with Alzheimer's disease stage and correlate strongly with tau, a protein whose accumulation is a hallmark of the disease.
How strong is the evidence linking rs112259525 to Alzheimer's disease?
Evidence is preliminary. It comes from a single genome-wide association study of 1,001 participants, and no specific effect size for this variant was reported in the available study text. Independent replication has not been described in the provided literature.
Is rs112259525 the top hit in its GWAS?
No. The strongest association reported in that study was rs7232 in the MS4A6A gene on chromosome 11, which reached a false discovery rate of 3.01×10^-8. rs112259525 was among the other loci examined in the same analysis.