P4‐246: Analysis of two immune function genes (CR1 and CD2AP) in Alzheimer's disease in two large Canadian cohorts
Bibliographic record
Abstract
Complement Receptor 1 (CR1) and CD2-associated protein (CD2AP) are two immune function genes identified in genome-wide association studies as risk factors for late onset Alzheimer Disease (LOAD). Additionally, a recent study suggested that a missense single nucleotide polymorphism (SNP) in CR1 (rs4844609, Thr1610Ser) may be a causative pathological mutation associated with increase risk of AD. We investigated the risk of LOAD associated with SNPs in CR1 (rs 6656401, rs3818361, rs4844609) and CD2Ap (rs9349407) using two large Canadian cohorts from Canadian Study of Health and Aging (CSHA) and A Canadian Collaborative Cohort of Cognitive Impairment and Related Dementia (ACCORD). We combined samples from 2 large Canadian cohorts for analysis of genetic risks. We examined subjects age 65 and above only from the 2 cohorts: AD (n = 421) was diagnosed by NINCDS-ADRDA criteria, and controls (n = 612) were normal subjects who did not show any cognitive decline during the time of follow up. Genotypes were obtained using TaqMan assays, and chi-squared test was used to compare allele and genotype frequencies. Further stratified analyses were performed based on APOE E4 status, age, and sex, and adjusted odds ratios were obtained from logistic regression. We found significant allelic associations with rs6656401 (unadjusted P = 0.006) and with rs3818361 (unadjusted P = 0.037), but not with rs4844609 (unadjusted P = 0.98) nor with CD2Ap rs9349407 (unadjusted P = 0.465). Strong linkage disequilibrium was found between rs6656401 and rs4844609 (D' = 1.0), although the minor allele frequency of rs4844609 is very low (2.6%), and no homozygotes were found in our cohort. After adjustment for age and APOE genotype, only rs6656401 remained significant (P = 0.031) with O.R. 1.4 (95% C.I. 1.031-1.91). While we confirmed association of CR1 SNPs rs6656401 with LOAD, we could not demonstrate any significant association with rs4844609, suggesting that this is not a pathological SNP for LOAD. No significant association was found with CD2Ap in our cohort either. Further molecular studies with CR1 or another gene in close linkage disequilibrium to this locus may reveal mechanisms leading to elevated risk in LOAD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.005 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".