P1‐058: Genome‐wide association study in PET imaging longitudinal data
Bibliographic record
Abstract
Alzheimer's disease (AD) is a complex disease in which the quest for causative genes has been challenging. In this search, genome-wide studies (GWAS) have been a valuable tool, being able to investigate, through thousands of markers, associations with the disease or with its endophenotypes. However, GWAS analyses almost always use cross-sectional data. Despite the adversities of obtaining and analyzing longitudinal data, the information about the disease progress can be of great importance. For this reason, we have searched for genetic markers associated with changes in brain amyloid (Aβ) load and glucose uptake. [F]Florbetapir positron emission tomography (PET) imaging was employed to assess brain Aβ levels in 412 participants from the Alzheimer's Disease Neuroimaging Initiative, whilst glucose uptake was measured using [F]fludeoxyglucose PET (FDG) in 419 subjects from the same cohort. The genotypes were obtained with IlluminaHumanOmni2.5 beadchip. After quality control in both imaging and genetic data, a GWAS was performed. The phenotypes used were the differences between global SUVR in the baseline and 24 months follow-up of [F]florbetapir and FDG. Covariates as diagnostic status and baseline SUVR were added in the genetic analysis. The Bonferroni threshold of genome-wide significance is 3.9x10. Values higher then 3.9x10 but less then 10were considered trends of association. None of the SNPs reached genome-wide significance, however trends of association are reported here (Figure 1). Aβ accumulation shows a trend with 24 markers from 15 genes, in which probably the most relevant, and significant, is PLCH1. Brain hipometabolism indicate trend associations with 21 markers from 8 genes. The genes TTC39B and NRP1were the most significant. A) Quantile-quantile plot of [F]florbetabir GWAS. B) Manhattan plot [F]florbetabir GWAS. Red line represents the trend threshold of significance. C) Quantile-quantile plot of FDG GWAS. D) Manhattan plot FDG GWAS. Red line represents the trend threshold of significance. The major genes reported to be associated with AD were not found in the present study. Interestingly, Aβ accumulation seems to be related to the PLCH1 gene, which encodes for a phospholipase-C family-member. Phospholipases are important enzymes with key roles in cell signaling. Another relevant result may be the association of hypometabolism with the TTC39B gene. Its function is not clear, however this gene has been related to lipid metabolism. Further studies with bigger sample size would be necessary to confirm present results.
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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 | 0.007 | 0.017 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.027 | 0.004 |
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".