ArticleTranslational psychiatry2022
Allele-specific analysis reveals exon- and cell-type-specific regulatory effects of Alzheimer's disease-associated genetic variants.
Article in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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
17 citing papers in PubMed, 25 citations in OpenAlex.
- Allele specific expression in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Distinct Regulatory Genomic Architectures Distinguish Early-Onset from Late-Onset Alzheimer's Disease.Genes · 2026Article
- Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Molecular Mechanisms of Perivascular Macrophages in Alzheimer's Disease: Insights from Single-Cell Sequencing and Mendelian Randomization.Cellular and molecular neurobiology · 2025Article
- Identification of diagnostic DNA methylation markers in the blood of Japanese Alzheimer's disease patients using methylation capture sequencing.Clinical epigenetics · 2025Article
- Computational methods for allele-specific expression in single cells.Trends in genetics : TIG · 2024Review
- Whole exome sequencing analyses identified novel genes for Alzheimer's disease and related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Identification of a specific APOE transcript and functional elements associated with Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Cell type-specific functions of Alzheimer's disease endocytic risk genes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Leveraging molecular quantitative trait loci to comprehend complex diseases/traits from the omics perspective.Human genetics · 2023Review
- Bioinformatics pipeline to guide post-GWAS studies in Alzheimer's: A new catalogue of disease candidate short structural variants.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Expression ofGenes · 2023Article
- ipaQTL-atlas: an atlas of intronic polyadenylation quantitative trait loci across human tissues.Nucleic acids research · 2023Article
- A role of inflammaging in aortic aneurysm: new insights from bioinformatics analysis.Frontiers in immunology · 2023Article
- Analyzing alternative splicing in Alzheimer's disease postmortem brain: a cell-level perspective.Frontiers in molecular neuroscience · 2023Article
- Brain Region-Dependent Alternative Splicing of Alzheimer Disease (AD)-Risk Genes Is Associated With Neuropathological Features in AD.International neurourology journal · 2022Article
- The relationships between neuroglial and neuronal changes in Alzheimer's disease, and the related controversies II:Journal of central nervous system disease · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Elucidating regulatory effects of Alzheimer's disease (AD)-associated genetic variants is critical for unraveling their causal pathways and understanding the pathology. However, their cell-type-specific regulatory mechanisms in the brain remain largely unclear. Here, we conducted an analysis of allele-specific expression quantitative trait loci (aseQTLs) for 33 AD-associated variants in four brain regions and seven cell types using ~3000 bulk RNA-seq samples and >0.25 million single nuclei. We first develop a flexible hierarchical Poisson mixed model (HPMM) and demonstrate its superior statistical power to a beta-binomial model achieved by unifying samples in both allelic and genotype-level expression data. Using the HPMM, we identified 24 (~73%) aseQTLs in at least one brain region, including three new eQTLs associated with CA12, CHRNE, and CASS4. Notably, the APOE ε4 variant reduces APOE expression across all regions, even in AD-unaffected controls. Our results reveal region-dependent and exon-specific effects of multiple aseQTLs, such as rs2093760 with CR1, rs7982 with CLU, and rs3865444 with CD33. In an attempt to pinpoint the cell types responsible for the observed tissue-level aseQTLs using the snRNA-seq data, we detected many aseQTLs in microglia or monocytes associated with immune-related genes, including HLA-DQB1, HLA-DQA2, CD33, FCER1G, MS4A6A, SPI1, and BIN1, highlighting the regulatory role of AD-associated variants in the immune response. These findings provide further insights into potential causal pathways and cell types mediating the effects of the AD-associated variants.
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.