ArticlePacific Symposium on Biocomputing. Pacific Symposium on Biocomputing2023
Polygenic resilience score may be sensitive to preclinical Alzheimer's disease changes.
Article in Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 2 citations in OpenAlex.
- Polygenic risk scores in human genetics for study design discovery and translation.Human genetics · 2026Review
- Improved polygenic risk prediction for alzheimer's disease and related dementias using deep learning: age and APOE-stratified analysis.Alzheimer's research & therapy · 2026Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Late-onset Alzheimer's disease (LOAD) is a polygenic disorder with a long prodromal phase, making early diagnosis challenging. Twin studies estimate LOAD as 60-80% heritable, and while common genetic variants can account for 30% of this heritability, nearly 70% remains "missing". Polygenic risk scores (PRS) leverage combined effects of many loci to predict LOAD risk, but often lack sensitivity to preclinical disease changes, limiting clinical utility. Our group has built and published on a resilience phenotype to model better-than-expected cognition give amyloid pathology burden and hypothesized it may assist in preclinical polygenic risk prediction. Thus, we built a LOAD PRS and a resilience PRS and evaluated both in predicting cognition in a dementia-free cohort (N=254). The LOAD PRS had a significant main effect on baseline memory (β=-0.18, P=1.68E-03). Both the LOAD PRS (β=-0.03, P=1.19E-03) and the resilience PRS (β=0.02, P=0.03) had significant main effects on annual memory decline. The resilience PRS interacted with CSF Aβ on baseline memory (β=-6.04E-04, P=0.02), whereby it predicted baseline memory among Aβ+ individuals (β=0.44, P=0.01) but not among Aβ- individuals (β=0.06, P=0.46). Excluding APOE from PRS resulted in mainly LOAD PRS associations attenuating, but notably the resilience PRS interaction with CSF Aβ and selective prediction among Aβ+ individuals was consistent. Although the resilience PRS is currently somewhat limited in scope from the phenotype's cross-sectional nature, our results suggest that the resilience PRS may be a promising tool in assisting in preclinical disease risk prediction among dementia-free and Aβ+ individuals, though replication and fine-tuning are needed.
Indexed as
Identifiers
36540999PMC9888419W4309849954What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.