SynthesisMolecular psychiatry2022
Whole-genome sequencing reveals novel ethnicity-specific rare variants associated with Alzheimer's disease.
Synthesis in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Genetic background and multidomain interventions in mild cognitive impairment.Alzheimer's research & therapy · 2025Trial
- Genetic Investigation of Corrected QT Interval Sensitivity to Oral Bepridil Hydrochloride Hydrate in Patients With Atrial Fibrillation.Journal of the American Heart Association · 2026Article
- Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias.medRxiv : the preprint server for health sciences · 2026Article
- Whole-genome sequencing reveals an East Asian-specific rare variant of INPP5J associated with Alzheimer's disease.Translational psychiatry · 2026Article
- Genetic association analyses of cognitive performance across multi-ancestry older adults: Application of Tobit models.Journal of Alzheimer's disease : JAD · 2025Article
- New insights into the 17β-hydroxysteroid dehydrogenase type 10 and amyloid-β 42 derived cytotoxicity relevant to Alzheimer's disease.Alzheimer's research & therapy · 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
- Genetic Links Between Subcortical Brain Morphometry and Suicide Attempt Risk in Children and Adults.Human brain mapping · 2025Article
- Navigating the blurred boundary: Neuropathologic changes versus clinical symptoms in Alzheimer's disease, and its consequences for research in genetics.Journal of Alzheimer's disease : JAD · 2025Review
- An ontology-based rare disease common data model harmonising international registries, FHIR, and Phenopackets.Scientific data · 2025Article
- Exploring the Interconnections of Genetic, Lifestyle, and Epigenetic Influences on Brain Aging: A Comprehensive Review.Current Alzheimer research · 2025Review
- Fast and accurate DNASeq variant calling workflow composed of LUSH toolkit.Human genomics · 2024Article
- Investigating Causal Associations between the Gut Microbiota and Dementia: A Mendelian Randomization Study.Nutrients · 2024Article
- GWAS advancements to investigate disease associations and biological mechanisms.Clinical and translational discovery · 2024Article
- Key variants via the Alzheimer's Disease Sequencing Project whole genome sequence data.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- CRISPR/Cas9-mediated knock-in cells of the late-onset Alzheimer's disease-risk variant, SHARPIN G186R, reveal reduced NF-κB pathway and accelerated Aβ secretion.Journal of human genetics · 2024Article
- Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The HLA-DRB1*09:01-DQB1*03:03 haplotype is associated with the risk for late-onset Alzheimer's disease in APOEnpj aging · 2024Article
- Integrated genomic, proteomic and cognitive assessment in Duchenne Muscular Dystrophy suggest astrocyte centric pathology.Heliyon · 2023Article
- Co-Expression Network Analysis Identifies Molecular Determinants of Loneliness Associated with Neuropsychiatric and Neurodegenerative Diseases.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is the most common multifactorial neurodegenerative disease among elderly people. Genome-wide association studies (GWAS) have been highly successful in identifying genetic risk factors. However, GWAS investigate common variants, which tend to have small effect sizes, and rare variants with potentially larger phenotypic effects have not been sufficiently investigated. Whole-genome sequencing (WGS) enables us to detect those rare variants. Here, we performed rare-variant association studies by using WGS data from 140 individuals with probable AD and 798 cognitively normal elder controls (CN), as well as single-nucleotide polymorphism genotyping data from an independent large Japanese AD cohort of 1604 AD and 1235 CN subjects. We identified two rare variants as candidates for AD association: a missense variant in OR51G1 (rs146006146, c.815 G > A, p.R272H) and a stop-gain variant in MLKL (rs763812068, c.142 C > T, p.Q48X). Subsequent in vitro functional analysis revealed that the MLKL stop-gain variant can contribute to increases not only in abnormal cells that should die by programmed cell death but do not, but also in the ratio of Aβ42 to Aβ40. We further detected AD candidate genes through gene-based association tests of rare variants; a network-based meta-analysis using these candidates identified four functionally important hub genes (NCOR2, PLEC, DMD, and NEDD4). Our findings will contribute to the understanding of AD and provide novel insights into its pathogenic mechanisms that can be used in future studies.
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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.