Prioritization of Genetic Variants in the microRNA Regulome as Functional Candidates in Genome-Wide Association Studies

Authors

  • Brendan Bulik-Sullivan,

    1. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Sara Selitsky,

    1. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Praveen Sethupathy

    Corresponding author
    1. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
    2. Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
    3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
    • Correspondence to: Praveen Sethupathy, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail: praveen_sethupathy@med.unc.edu

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  • Communicated by Arupa Ganguly

  • [The copyright line for this article was changed on 9 June 2014 after original online publication.]

ABSTRACT

Comprehensive analyses of results from genome-wide association studies (GWAS) have demonstrated that complex disease/trait-associated loci are enriched in gene regulatory regions of the genome. The search for causal regulatory variation has focused primarily on transcriptional elements, such as promoters and enhancers. microRNAs (miRNAs) are now widely appreciated as critical posttranscriptional regulators of gene expression and are thought to impart stability to biological systems. Naturally occurring genetic variation in the miRNA regulome is likely an important contributor to phenotypic variation in the human population. However, the extent to which polymorphic miRNA-mediated gene regulation underlies GWAS signals remains unclear. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the miRNA regulome as functional candidates in GWAS. We highlight specific findings, including a variant in the promoter of the miRNA let-7 that may contribute to human height variation. We also provide a discussion of how our approach can be expanded in the future. Overall, we believe that the results of this study will be valuable for researchers interested in determining whether GWAS signals implicate the miRNA regulome in their disease/trait of interest.

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