دورية أكاديمية
أعرض في EDS

Genome-wide association study of neocortical Lewy-related pathology.

التفاصيل البيبلوغرافية
العنوان: Genome-wide association study of neocortical Lewy-related pathology.
المؤلفون: Peuralinna T; Molecular Neurology, Research Program Unit, Biomedicum, University of Helsinki Helsinki, Finland., Myllykangas L; Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB Helsinki, Finland ; Folkhalsan Institute of Genetics Helsinki, Finland., Oinas M; Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB Helsinki, Finland ; Department of Neurosurgery, Helsinki University Central Hospital Helsinki, Finland., Nalls MA; Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, NIH Bethesda, Maryland., Keage HA; School of Psychology, Social Work and Social Policy, University of South Australia Adelaide, Australia ; Department of Public Health and Primary Care, University of Cambridge Cambridge, United Kingdom., Isoviita VM; Molecular Neurology, Research Program Unit, Biomedicum, University of Helsinki Helsinki, Finland., Valori M; Molecular Neurology, Research Program Unit, Biomedicum, University of Helsinki Helsinki, Finland., Polvikoski T; Institute for Ageing and Health, Newcastle University Newcastle, United Kingdom., Paetau A; Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB Helsinki, Finland., Sulkava R; School of Public Health and Clinical Nutrition, University of Eastern Finland Kuopio, Finland., Ince PG; Department of Neuroscience, University of Sheffield Sheffield, United Kingdom., Zaccai J; Department of Public Health and Primary Care, University of Cambridge Cambridge, United Kingdom., Brayne C; Department of Public Health and Primary Care, University of Cambridge Cambridge, United Kingdom., Traynor BJ; Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, NIH Bethesda, Maryland., Hardy J; Reta Lila Weston Research Laboratories, Departments of Molecular Neuroscience and of Clinical Neuroscience, UCL Institute of Neurology Queen Square, London, United Kingdom., Singleton AB; Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, NIH Bethesda, Maryland., Tienari PJ; Molecular Neurology, Research Program Unit, Biomedicum, University of Helsinki Helsinki, Finland ; Department of Neurology, Helsinki University Central Hospital Helsinki, Finland.
المصدر: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2015 Sep; Vol. 2 (9), pp. 920-31. Date of Electronic Publication: 2015 Aug 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley Periodicals, Inc on behalf of American Neurological Association Country of Publication: United States NLM ID: 101623278 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2328-9503 (Print) Linking ISSN: 23289503 NLM ISO Abbreviation: Ann Clin Transl Neurol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Hoboken, NJ] : Wiley Periodicals, Inc on behalf of American Neurological Association, [2014]-
مستخلص: Objective: Dementia 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.
Methods: LRP 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).
Results: By 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.
Interpretation: We 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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معلومات مُعتمدة: ZIA AG000932 United States ImNIH Intramural NIH HHS; MR/L022656/1 United Kingdom MRC_ Medical Research Council; MR/L016451/1 United Kingdom MRC_ Medical Research Council; G1100540 United Kingdom MRC_ Medical Research Council; G0900652 United Kingdom MRC_ Medical Research Council; G9901400 United Kingdom MRC_ Medical Research Council; G0400074 United Kingdom MRC_ Medical Research Council; G0502157 United Kingdom MRC_ Medical Research Council; G0900582 United Kingdom MRC_ Medical Research Council; Z01 AG000950 United States ImNIH Intramural NIH HHS
تواريخ الأحداث: Date Created: 20150925 Date Completed: 20150924 Latest Revision: 20220311
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4574809
DOI: 10.1002/acn3.231
PMID: 26401513
قاعدة البيانات: MEDLINE
الوصف
تدمد:2328-9503
DOI:10.1002/acn3.231