ArticleAnnals of clinical and translational neurology2015
Genome-wide association study of neocortical Lewy-related pathology.
Article in Annals of clinical and translational neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Impaired Aggrephagy, Interrupted Vesicular Trafficking, and Cellular Stress, Lead to Protein Aggregation, and Synaptic Dysfunction in Cerebellum of Children and Adults with Idiopathic Autism.Cerebellum (London, England) · 2025Article
- Genetic risk and plasma biomarkers of dementia with Lewy bodies in a Chinese population.NPJ Parkinson's disease · 2025Article
- Involvement of ApoE4 in dementia with Lewy bodies in the prodromal and demented stages: evaluation of the Strasbourg cohort.GeroScience · 2024Article
- A cross-tissue transcriptome-wide association study identifies new susceptibility genes for frailty.Frontiers in genetics · 2024Article
- Recent advances in novel mutation genes of Parkinson's disease.Journal of neurology · 2023Review
- Spectrins: molecular organizers and targets of neurological disorders.Nature reviews. Neuroscience · 2023Review
- α-Synuclein Promotes Neuronal Dysfunction and Death by Disrupting the Binding of Ankyrin to β-Spectrin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Genetics of synucleins in neurodegenerative diseases.Acta neuropathologica · 2021Review
- The Spread of Spectrin in Ataxia and Neurodegenerative Disease.Journal of experimental neurology · 2021Article
- βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases.International journal of biological sciences · 2021Review
- Pathological Influences on Clinical Heterogeneity in Lewy Body Diseases.Movement disorders : official journal of the Movement Disorder Society · 2020Review
- Lewy-related pathology exhibits two anatomically and genetically distinct progression patterns: a population-based study of Finns aged 85.Acta neuropathologica · 2019Article
- Article
- A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.Acta neuropathologica · 2019Article
- A comprehensive screening of copy number variability in dementia with Lewy bodies.Neurobiology of aging · 2019Article
- Early microglial activation and peripheral inflammation in dementia with Lewy bodies.Brain : a journal of neurology · 2018Article
- Dementia with Lewy bodies and Parkinson's disease-dementia: current concepts and controversies.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Alzheimer risk loci and associated neuropathology in a population-based study (Vantaa 85+).Neurology. Genetics · 2018Article
- α-synuclein Induces Mitochondrial Dysfunction through Spectrin and the Actin Cytoskeleton.Neuron · 2018Article
- Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study.The Lancet. Neurology · 2018Article
Corrections and comments
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Authors and funding
17 authors at 10 institutions in 4 countries.
Funding
Abstract
objectiveDementia with Lewy bodies is an α-synucleinopathy characterized by neocortical Lewy-related pathology (LRP). We carried out a genome-wide association study (GWAS) on neocortical LRP in a population-based sample of subjects aged 85 or over.
methodsLRP was analyzed in 304 subjects in the Vantaa 85+ sample from Southern Finland. The GWAS included 41 cases with midbrain, hippocampal, and neocortical LRP and 177 controls without midbrain and hippocampal LRP. The Medical Research Council Cognitive Function and Ageing Study (CFAS) material was used for replication (51 cases and 131 controls).
resultsBy analyzing 327,010 markers the top signal was obtained at the HLA-DPA1/DPB1 locus (P = 1.29 × 10(-7)); five other loci on chromosomes 15q14, 2p21, 2q31, 18p11, and 5q23 were associated with neocortical LRP at P < 10(-5). Two loci were marked by multiple markers, 2p21 (P = 3.9 × 10(-6), upstream of the SPTBN1 gene), and HLA-DPA1/DPB1; these were tested in the CFAS material. Single marker (P = 0.0035) and haplotype (P = 0.04) associations on 2p21 were replicated in CFAS, whereas HLA-DPA1/DPB1 association was not. Bioinformatic analyses suggest functional effects for the HLA-DPA1/DPB1 markers as well as the 15q14 marker rs8037309.
interpretationWe identified suggestive novel risk factors for neocortical LRP. SPTBN1 is the candidate on 2p21, it encodes beta-spectrin, an α-synuclein binding protein and a component of Lewy bodies. The HLA-DPA1/DPB1 association suggests a role for antigen presentation or alternatively, cis-regulatory effects, one of the regulated neighboring genes identified here (vacuolar protein sorting 52) plays a role in vesicular trafficking and has been shown to interact with α-synuclein in a yeast model.
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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.