دورية أكاديمية
أعرض في EDS

Human pancreatic islet microRNAs implicated in diabetes and related traits by large-scale genetic analysis.

التفاصيل البيبلوغرافية
العنوان: Human pancreatic islet microRNAs implicated in diabetes and related traits by large-scale genetic analysis.
المؤلفون: Taylor HJ; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892.; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0BB, UK.; Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0BB, UK., Hung YH; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853., Narisu N; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892., Erdos MR; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892., Kanke M; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853., Yan T; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892., Grenko CM; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892., Swift AJ; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892., Bonnycastle LL; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892., Sethupathy P; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853., Collins FS; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892., Taylor DL; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Feb 14; Vol. 120 (7), pp. e2206797120. Date of Electronic Publication: 2023 Feb 09.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: MicroRNAs*/metabolism , Diabetes Mellitus, Type 2*/genetics , Diabetes Mellitus, Type 2*/metabolism , Islets of Langerhans*/metabolism, Humans ; Glycated Hemoglobin ; Quantitative Trait Loci/genetics
مستخلص: Genetic studies have identified ≥240 loci associated with the risk of type 2 diabetes (T2D), yet most of these loci lie in non-coding regions, masking the underlying molecular mechanisms. Recent studies investigating mRNA expression in human pancreatic islets have yielded important insights into the molecular drivers of normal islet function and T2D pathophysiology. However, similar studies investigating microRNA (miRNA) expression remain limited. Here, we present data from 63 individuals, the largest sequencing-based analysis of miRNA expression in human islets to date. We characterized the genetic regulation of miRNA expression by decomposing the expression of highly heritable miRNAs into cis- and trans- acting genetic components and mapping cis -acting loci associated with miRNA expression [miRNA-expression quantitative trait loci (eQTLs)]. We found i) 84 heritable miRNAs, primarily regulated by trans -acting genetic effects, and ii) 5 miRNA-eQTLs. We also used several different strategies to identify T2D-associated miRNAs. First, we colocalized miRNA-eQTLs with genetic loci associated with T2D and multiple glycemic traits, identifying one miRNA, miR-1908, that shares genetic signals for blood glucose and glycated hemoglobin (HbA1c). Next, we intersected miRNA seed regions and predicted target sites with credible set SNPs associated with T2D and glycemic traits and found 32 miRNAs that may have altered binding and function due to disrupted seed regions. Finally, we performed differential expression analysis and identified 14 miRNAs associated with T2D status-including miR-187-3p, miR-21-5p, miR-668, and miR-199b-5p-and 4 miRNAs associated with a polygenic score for HbA1c levels-miR-216a, miR-25, miR-30a-3p, and miR-30a-5p.
التعليقات: Erratum in: Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2302726120. (PMID: 36913595)
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معلومات مُعتمدة: ZIA HG000024 United States ImNIH Intramural NIH HHS
فهرسة مساهمة: Keywords: diabetes; eQTL; microRNA; pancreatic islets
المشرفين على المادة: 0 (MicroRNAs)
0 (Glycated Hemoglobin)
تواريخ الأحداث: Date Created: 20230209 Date Completed: 20230213 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC9963967
DOI: 10.1073/pnas.2206797120
PMID: 36757889
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.2206797120