ArticleNature communications2021
Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- Review
- Long-Read epigenetic clocks identify improved brain aging predictions.bioRxiv : the preprint server for biology · 2025Article
- Intron Retention and Alzheimer's Disease (AD): A Review of Regulation Genes Implicated in AD.Genes · 2025Review
- Identification of a specific APOE transcript and functional elements associated with Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Translational implications of CHRFAM7A, an elusive human-restricted fusion gene.Molecular psychiatry · 2024Review
- Cell type-specific roles of APOE4 in Alzheimer disease.Nature reviews. Neuroscience · 2024Review
- RExPRT: a machine learning tool to predict pathogenicity of tandem repeat loci.Genome biology · 2024Article
- Functional genomics provide key insights to improve the diagnostic yield of hereditary ataxia.Brain : a journal of neurology · 2023Article
- Leveraging omic features with F3UTER enables identification of unannotated 3'UTRs for synaptic genes.Nature communications · 2022Article
Corrections and comments
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Authors and funding
14 authors at 20 institutions in 13 countries.
Funding
Abstract
Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer's disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.
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Registered trials
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