• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    A transcription-centric model of SNP-age interaction

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Wang, Kun
    Basu, Mahashweta
    Malin, Justin
    Hannenhalli, Sridhar
    Date
    2021-03-26
    Journal
    PLoS Genetics
    Publisher
    Public Library of Science
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1371/journal.pgen.1009427
    Abstract
    Complex age-associated phenotypes are caused, in part, by an interaction between an individual’s genotype and age. The mechanisms governing such interactions are however not entirely understood. Here, we provide a novel transcriptional mechanism-based framework–SNiPage, to investigate such interactions, whereby a transcription factor (TF) whose expression changes with age (age-associated TF), binds to a polymorphic regulatory element in an allele-dependent fashion, rendering the target gene’s expression dependent on both, the age and the genotype. Applying SNiPage to GTEx, we detected ~637 significant TF-SNP-Gene triplets on average across 25 tissues, where the TF binds to a regulatory SNP in the gene’s promoter or putative enhancer and potentially regulates its expression in an age- and allele-dependent fashion. The detected SNPs are enriched for epigenomic marks indicative of regulatory activity, exhibit allele-specific chromatin accessibility, and spatial proximity to their putative gene targets. Furthermore, the TF-SNP interaction-dependent target genes have established links to aging and to age-associated diseases. In six hypertension-implicated tissues, detected interactions significantly inform hypertension state of an individual. Lastly, the age-interacting SNPs exhibit a greater proximity to the reported phenotype/diseases-associated SNPs than eSNPs identified in an interaction-independent fashion. Overall, we present a novel mechanism-based model, and a novel framework SNiPage, to identify functionally relevant SNP-age interactions in transcriptional control and illustrate their potential utility in understanding complex age-associated phenotypes.
    Keyword
    age-related disease
    Age Factors
    Aging--genetics
    Polymorphism, Genetic
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15084
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pgen.1009427
    Scopus Count
    Collections
    UMB Open Access Articles

    entitlement

    Related articles

    • Allele-specific transcriptional regulation of IRF4 in melanocytes is mediated by chromatin looping of the intronic rs12203592 enhancer to the IRF4 promoter.
    • Authors: Visser M, Palstra RJ, Kayser M
    • Issue date: 2015 May 1
    • An integrative functional genomics framework for effective identification of novel regulatory variants in genome-phenome studies.
    • Authors: Zhao J, Cheng F, Jia P, Cox N, Denny JC, Zhao Z
    • Issue date: 2018 Jan 29
    • Co-regulated transcripts associated to cooperating eSNPs define Bi-fan motifs in human gene networks.
    • Authors: Kreimer A, Pe'er I
    • Issue date: 2014 Sep
    • How to Use SNP_TATA_Comparator to Find a Significant Change in Gene Expression Caused by the Regulatory SNP of This Gene's Promoter via a Change in Affinity of the TATA-Binding Protein for This Promoter.
    • Authors: Ponomarenko M, Rasskazov D, Arkova O, Ponomarenko P, Suslov V, Savinkova L, Kolchanov N
    • Issue date: 2015
    • A New Mechanism for Mendelian Dominance in Regulatory Genetic Pathways: Competitive Binding by Transcription Factors.
    • Authors: Porter AH, Johnson NA, Tulchinsky AY
    • Issue date: 2017 Jan
    DSpace software (copyright © 2002 - 2022)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.