ArticlePloS one2023
What does heritability of Alzheimer's disease represent?
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Alzheimer disease is (sometimes) highly heritable: Drivers of variation in heritability estimates for binary traits, a systematic review.PLoS genetics · 2025Pooled it
- The role of genetically predicted serum iron levels on neurodegenerative and cardiovascular traits.Scientific reports · 2024Pooled it
- A new era of genome-wide association studies in the field of Alzheimer's disease and overlapping co-pathologies: lessons learned from a neuropathology-centered approach.Acta neuropathologica · 2026Review
- A novel method to disentangle tightly linked risk and resilience genes for brain disorders: application to Alzheimer's disease.Molecular psychiatry · 2026Article
- Cross-ancestry polygenic risk scores enhance Alzheimer's disease risk prediction in multiethnic cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- An empirical Bayes framework for burden and dispersion association tests helps prioritize rare variants associated with Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Dissecting Alzheimer's disease heritability across populations.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Short tandem repeat expansions in patients with neurodegenerative dementia.EBioMedicine · 2026Article
- Genetic Burden andJournal of personalized medicine · 2026Article
- Toward personalized medicine in AD/ADRD through genetic-exposome dementia risk assessments.NPJ dementia · 2026Review
- MAPT Haplotype Variation and Alzheimer's Disease Risk: A Narrative Review with Focus on the Jordanian Population.Current neuropharmacology · 2026Review
- Integrative analysis of cerebrospinal fluid biomarkers, metabolomics, and polygenic risk reveals novel metabolite associations with Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- Cross-Ancestry Polygenic Risk Scores Enhance Alzheimer's Disease Risk Prediction in Multiethnic Cohorts.medRxiv : the preprint server for health sciences · 2025Article
- Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations.Nature genetics · 2025Article
- Whole-genome sequencing analyses suggest novel genetic factors associated with Alzheimer's disease and a cumulative effects model for risk liability.Nature communications · 2025Article
- Alzheimer's disease and age-related macular degeneration: Shared and distinct immune mechanisms.Immunity · 2025Review
- Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.Molecular psychiatry · 2025Review
- Article
- Review
- Association of genetic risk of Alzheimer's disease and cognitive function in two European populations.Scientific reports · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
introductionBoth late-onset Alzheimer's disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the estimation of SNP-based heritability could explain the differences in reported heritability.
methodsWe compute heritability in five large independent cohorts (N = 7,396, 1,566, 803, 12,528 and 3,963) to determine whether a consensus for the AD heritability estimate can be reached. These cohorts vary by sample size, age of cases and controls and phenotype definition. We compute heritability a) for all SNPs, b) excluding APOE region, c) excluding both APOE and genome-wide association study hit regions, and d) SNPs overlapping a microglia gene-set.
resultsSNP-based heritability of late onset Alzheimer's disease is between 38 and 66% when age and genetic disease architecture are correctly accounted for. The heritability estimates decrease by 12% [SD = 8%] on average when the APOE region is excluded and an additional 1% [SD = 3%] when genome-wide significant regions were removed. A microglia gene-set explains 69-84% of our estimates of SNP-based heritability using only 3% of total SNPs in all cohorts.
conclusionThe heritability of neurodegenerative disorders cannot be represented as a single number, because it is dependent on the ages of cases and controls. Genome-wide association studies pick up a large proportion of total AD heritability when age and genetic architecture are correctly accounted for. Around 13% of SNP-based heritability can be explained by known genetic loci and the remaining heritability likely resides around microglial related genes.
Indexed as
Identifiers
What 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.