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dc.contributor.authorWang, Kun
dc.contributor.authorBasu, Mahashweta
dc.contributor.authorMalin, Justin
dc.contributor.authorHannenhalli, Sridhar
dc.date.accessioned2021-04-05T18:58:27Z
dc.date.available2021-04-05T18:58:27Z
dc.date.issued2021-03-26
dc.identifier.urihttp://hdl.handle.net/10713/15084
dc.description.abstractComplex 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.en_US
dc.description.urihttps://doi.org/10.1371/journal.pgen.1009427en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS Geneticsen_US
dc.subjectage-related diseaseen_US
dc.subject.meshAge Factorsen_US
dc.subject.meshAging--geneticsen_US
dc.subject.meshPolymorphism, Geneticen_US
dc.titleA transcription-centric model of SNP-age interactionen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pgen.1009427
dc.identifier.pmid33770080
dc.source.volume17
dc.source.issue3
dc.source.beginpagee1009427
dc.source.endpage
dc.source.countryUnited States


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