دورية أكاديمية
أعرض في EDS

Single-cell epigenomic analyses implicate candidate causal variants at inherited risk loci for Alzheimer's and Parkinson's diseases.

التفاصيل البيبلوغرافية
العنوان: Single-cell epigenomic analyses implicate candidate causal variants at inherited risk loci for Alzheimer's and Parkinson's diseases.
المؤلفون: Corces MR; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA., Shcherbina A; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Kundu S; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Department of Computer Science, Stanford University, Stanford, CA, USA., Gloudemans MJ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA., Frésard L; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA., Granja JM; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Program in Biophysics, Stanford University, Stanford, CA, USA., Louie BH; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA., Eulalio T; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA., Shams S; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Bagdatli ST; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Mumbach MR; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Liu B; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Biology, Stanford University, Stanford, CA, USA.; Baidu Research, Sunnyvale, CA, USA., Montine KS; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA., Greenleaf WJ; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Department of Applied Physics, Stanford University, Stanford, CA, USA.; Chan Zuckerberg Biohub, San Francisco, CA, USA., Kundaje A; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Department of Computer Science, Stanford University, Stanford, CA, USA., Montgomery SB; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Chang HY; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA. howchang@stanford.edu.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.; Program in Epithelial Biology, Stanford University, Stanford, CA, USA. howchang@stanford.edu.; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. howchang@stanford.edu., Montine TJ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. tmontine@stanford.edu.
المصدر: Nature genetics [Nat Genet] 2020 Nov; Vol. 52 (11), pp. 1158-1168. Date of Electronic Publication: 2020 Oct 26.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Co., c1992-
مواضيع طبية MeSH: Alzheimer Disease/*genetics , Brain/*anatomy & histology , Neurons/*physiology , Parkinson Disease/*genetics, Adult ; Atlases as Topic ; Biological Variation, Population ; Chromatin Assembly and Disassembly ; Cohort Studies ; Enhancer Elements, Genetic ; Epigenomics ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Haplotypes ; Humans ; Machine Learning ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; tau Proteins/genetics
مستخلص: Genome-wide association studies of neurological diseases have identified thousands of variants associated with disease phenotypes. However, most of these variants do not alter coding sequences, making it difficult to assign their function. Here, we present a multi-omic epigenetic atlas of the adult human brain through profiling of single-cell chromatin accessibility landscapes and three-dimensional chromatin interactions of diverse adult brain regions across a cohort of cognitively healthy individuals. We developed a machine-learning classifier to integrate this multi-omic framework and predict dozens of functional SNPs for Alzheimer's and Parkinson's diseases, nominating target genes and cell types for previously orphaned loci from genome-wide association studies. Moreover, we dissected the complex inverted haplotype of the MAPT (encoding tau) Parkinson's disease risk locus, identifying putative ectopic regulatory interactions in neurons that may mediate this disease association. This work expands understanding of inherited variation and provides a roadmap for the epigenomic dissection of causal regulatory variation in disease.
التعليقات: Comment in: Mov Disord. 2021 Feb;36(2):347. doi: 10.1002/mds.28481. (PMID: 33458867)
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معلومات مُعتمدة: RM1 HG007735 United States HG NHGRI NIH HHS; R00 AG059918 United States AG NIA NIH HHS; U01 HG009431 United States HG NHGRI NIH HHS; P30 AG066515 United States AG NIA NIH HHS; K99 AG059918 United States AG NIA NIH HHS; United States HHMI Howard Hughes Medical Institute; P50 AG005136 United States AG NIA NIH HHS; UF1 AG057707 United States AG NIA NIH HHS; P50 HG007735 United States HG NHGRI NIH HHS; T15 LM007033 United States LM NLM NIH HHS; P30 AG019610 United States AG NIA NIH HHS; S10 OD018220 United States OD NIH HHS; RF1 AG053959 United States AG NIA NIH HHS; S10 OD025212 United States OD NIH HHS; P50 NS062684 United States NS NINDS NIH HHS; P30 AG066509 United States AG NIA NIH HHS; P50 AG047366 United States AG NIA NIH HHS; R01 AG066490 United States AG NIA NIH HHS
المشرفين على المادة: 0 (MAPT protein, human)
0 (tau Proteins)
تواريخ الأحداث: Date Created: 20201027 Date Completed: 20201229 Latest Revision: 20240604
رمز التحديث: 20240604
مُعرف محوري في PubMed: PMC7606627
DOI: 10.1038/s41588-020-00721-x
PMID: 33106633
قاعدة البيانات: MEDLINE
الوصف
تدمد:1546-1718
DOI:10.1038/s41588-020-00721-x