ArticlePLoS genetics2022
Integrated analysis of direct and proxy genome wide association studies highlights polygenicity of Alzheimer's disease outside of the APOE region.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias.Nature genetics · 2026Pooled it
- Alzheimer disease is (sometimes) highly heritable: Drivers of variation in heritability estimates for binary traits, a systematic review.PLoS genetics · 2025Pooled it
- APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Crystallized and fluid cognitive abilities have different genetic associations with neuropsychiatric disorders.Nature communications · 2026Article
- Downward bias in the association between APOE and Alzheimer's disease using prevalent and by-proxy disease sampling in the All of Us research program.BMC medical genomics · 2026Article
- Article
- Integrative Genetic, Proteogenomic, and Multi-omics Analyses Reveal Sex-Biased Causal Genes and Drug Targets in Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2025Article
- Distinguishing specific from broad genetic associations between external correlates and common factors.Bioinformatics (Oxford, England) · 2025Article
- Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementia.medRxiv : the preprint server for health sciences · 2025Article
- Novel modelling approaches to elucidate the genetic architecture of resilience to Alzheimer's disease.Brain : a journal of neurology · 2025Article
- Robust Increase in IQCK Protein Expression in Mouse Models of Alzheimer's Disease and iPSC-Derived Neurons.Journal of cellular and molecular medicine · 2025Article
- Woolf et al's "GWAS by subtraction" is not useful for cross-generational Mendelian randomization studies.BMC research notes · 2025Article
- Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.Brain sciences · 2025Review
- Article
- Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.PloS one · 2025Article
- Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease.Nature genetics · 2024Article
- DINGO: increasing the power of locus discovery in maternal and fetal genome-wide association studies of perinatal traits.Nature communications · 2024Article
- Interpretation of 10 years of Alzheimer's disease genetic findings in the perspective of statistical heterogeneity.Briefings in bioinformatics · 2024Review
- Mendelian Randomization of Blood Metabolites Suggests Circulating Glutamine Protects Against Late-Onset Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Genetic Architecture of Neurological Disorders and Their Endophenotypes: Insights from Genetic Association Studies.Current topics in behavioral neurosciences · 2024Review
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5 authors.
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Abstract
Recent meta-analyses combining direct genome-wide association studies (GWAS) with those of family history (GWAX) have indicated very low SNP heritability of Alzheimer's disease (AD). These low estimates may call into question the prospects of continued progress in genetic discovery for AD within the spectrum of common variants. We highlight dramatic downward biases in previous methods, and we validate a novel method for the estimation of SNP heritability via integration of GWAS and GWAX summary data. We apply our method to investigate the genetic architecture of AD using GWAX from UK Biobank and direct case-control GWAS from the International Genomics of Alzheimer's Project (IGAP). We estimate the liability scale common variant SNP heritability of Clinical AD outside of APOE region at ~7-11%, and we project the corresponding estimate for AD pathology to be up to approximately 23%. We estimate that nearly 90% of common variant SNP heritability of Clinical AD exists outside the APOE region. Rare variants not tagged in standard GWAS may account for additional variance. Our results indicate that, while GWAX for AD in UK Biobank may result in greater attenuation of genetic effects beyond that conventionally assumed, it does not introduce appreciable contamination of signal by genetically distinct traits relative to direct case-control GWAS in IGAP. Genetic risk for AD represents a strong effect of APOE superimposed upon a highly polygenic background.
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