Genome-Wide Association Studies for Cerebrospinal Fluid Soluble TREM2 in Alzheimer’s Disease
Bibliographic record
Abstract
Alzheimer’s disease (AD) is the most common form of dementia. Rare variants in triggering receptor expressed on myeloid cells 2 (TREM2) have been identified as risk factors for AD. Soluble TREM2 (sTREM2) in the cerebrospinal fluid (CSF) is a potential and novel biomarker of neuroinflammation implicated in the onset and progression of AD. To explore the roles of CSF sTREM2 on the pathogenesis of AD, we performed genome-wide association studies (GWAS) by using the data from Alzheimer’s Disease Neuroimaging Initiative (ADNI). We found CSF sTREM2 levels were elevated with the disease stages, but there was no significant difference between that of AD patients and normal participants. CSF sTREM2 was positively correlated with CSF total tau and phosphorylated-tau levels (ρ>0.35, p0.32, p<1e-05, respectively) for all disease states. We identified the most significant CSF sTREM2 related locus was rs7232 (FDR=3.01e-08), a missense variant in MS4A6A gene of chromosome 11. Moreover, we also detected rs7232 was highly associated with MS4A6A gene expression (FDR=1.37e-18). In addition, our pathway analysis for our significant GWAS results showed that biological processes for regulation of viruses and immune response were highly overrepresented or enriched. Our study suggests that CSF sTREM2 plays an informative role in AD progression. Moreover, CSF sTREM2 and AD is highly related to viral infections and immune response.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".