ArticleJournal of human genetics2022
A functional variant of SHARPIN confers increased risk of late-onset Alzheimer's disease.
Article in Journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- NF-κB across the Alzheimer disease spectrum: Context-dependent protective and pathogenic roles.IBRO neuroscience reports · 2026Review
- Ethnic-specific effects of the LILRB2-LILRB5 locus and newly identified risk loci for Alzheimer's disease in the East Asian population.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetic association analyses of cognitive performance across multi-ancestry older adults: Application of Tobit models.Journal of Alzheimer's disease : JAD · 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
- Identification of novel candidate loci for Alzheimer's disease and related dementias by leveraging the shared genetic basis with hippocampal volume.Aging brain · 2025Article
- Met1-linked ubiquitination in cell signaling regulation.Biophysics reports · 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
- Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- Involvement of heterologous ubiquitination including linear ubiquitination in Alzheimer's disease and amyotrophic lateral sclerosis.Frontiers in molecular biosciences · 2023Review
- Identification of potential blood biomarkers for early diagnosis of Alzheimer's disease through immune landscape analysis.npj aging · 2022Article
- Cell Death-Related Ubiquitin Modifications in Inflammatory Syndromes: From Mice to Men.Biomedicines · 2022Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Late-onset Alzheimer's disease (LOAD) is the most common form of dementia, and its pathogenesis is multifactorial. We previously reported a rare functional variant of SHARPIN (rs572750141, NP_112236.3:p.Gly186Arg) that was significantly associated with LOAD. In addition, several recent studies have suggested the potential role of SHARPIN in AD pathogenesis. In this study, we sought to identify additional functional variants of SHARPIN in Japanese population. Six highly deleterious variants of SHARPIN, comprising four missense variants, one frameshift variant, and one stop-gain variant were detected from whole-genome sequencing data for 180 patients with LOAD and 184 with mild cognitive impairment. One of these candidate variants (rs77359862, NP_112236.3:p.Arg274Trp) was significantly associated with an increased risk of LOAD in 5043 LOAD cases and 11984 controls (P = 0.0016, odds ratio = 1.43). Furthermore, this variant SHARPIN showed aberrant cellular localization and reduced the activation of NF-κB, a central mediator of inflammatory and immune responses. Further investigation of the physiologic role of SHARPIN may reveal the mechanism of onset of LOAD.
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