دورية أكاديمية
أعرض في EDS

Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease.

التفاصيل البيبلوغرافية
العنوان: Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease.
المؤلفون: Branciamore S; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA., Gogoshin G; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA., Rodin AS; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA. arodin@coh.org., Myers AJ; Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. profmyersUM@gmail.com.; Institute for Data Science and Computing, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. profmyersUM@gmail.com.; Interdepartmental Program in Neuroscience, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. profmyersUM@gmail.com.; Interdepartmental Program in Human Genetics and Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. profmyersUM@gmail.com.
المصدر: Scientific reports [Sci Rep] 2024 Jun 28; Vol. 14 (1), pp. 14954. Date of Electronic Publication: 2024 Jun 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Alzheimer Disease*/genetics , Alzheimer Disease*/metabolism , Apolipoprotein E4*/genetics , Genetic Predisposition to Disease*, Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Alleles ; Bayes Theorem ; Haplotypes ; HLA-DR alpha-Chains/genetics ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Risk Factors
مستخلص: While there are currently over 40 replicated genes with mapped risk alleles for Late Onset Alzheimer's disease (LOAD), the Apolipoprotein E locus E4 haplotype is still the biggest driver of risk, with odds ratios for neuropathologically confirmed E44 carriers exceeding 30 (95% confidence interval 16.59-58.75). We sought to address whether the APOE E4 haplotype modifies expression globally through networks of expression to increase LOAD risk. We have used the Human Brainome data to build expression networks comparing APOE E4 carriers to non-carriers using scalable mixed-datatypes Bayesian network (BN) modeling. We have found that VGF had the greatest explanatory weight. High expression of VGF is a protective signal, even on the background of APOE E4 alleles. LOAD risk signals, considering an APOE background, include high levels of SPECC1L, HLA-DRA and RANBP3L. Our findings nominate several new transcripts, taking a combined approach to network building including known LOAD risk loci.
(© 2024. The Author(s).)
التعليقات: Update of: Res Sq. 2023 Dec 14:rs.3.rs-3678057. doi: 10.21203/rs.3.rs-3678057/v1. (PMID: 38168398)
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معلومات مُعتمدة: AG069008 United States AG NIA NIH HHS; P50 AG005128 United States AG NIA NIH HHS; P50 AG005146 United States AG NIA NIH HHS; P50 AG005136 United States AG NIA NIH HHS; P30 AG010161 United States AG NIA NIH HHS; R01 LM013138 United States LM NLM NIH HHS; P50 AG005144 United States AG NIA NIH HHS; P30 CA033572 United States CA NCI NIH HHS; P30 AG019610 United States AG NIA NIH HHS; P30 AG053760 United States AG NIA NIH HHS; P50 MH060451 United States MH NIMH NIH HHS; R01LM013138 United States LM NLM NIH HHS; P30CA033572 United States CA NCI NIH HHS; U01 AG016976 United States AG NIA NIH HHS; P50 NS039764 United States NS NINDS NIH HHS; P50 AG005681 United States AG NIA NIH HHS; P30 AG013846 United States AG NIA NIH HHS; R01 AG069008 United States AG NIA NIH HHS; P50 AG016570 United States AG NIA NIH HHS; P50 AG005134 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: APOE E4; Apolipoprotein E; Bayesian networks; Gene expression; Genetics; Late Onset Alzheimer's disease
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Apolipoprotein E4)
0 (HLA-DR alpha-Chains)
0 (Nuclear Proteins)
0 (RanBP3L protein, human)
0 (SPECC1L protein, human)
0 (VGF protein, human)
تواريخ الأحداث: Date Created: 20240628 Date Completed: 20240628 Latest Revision: 20240710
رمز التحديث: 20240711
مُعرف محوري في PubMed: PMC11213882
DOI: 10.1038/s41598-024-65010-7
PMID: 38942763
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-024-65010-7