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Prioritization of Genetic Variants in the micro RNA Regulome as Functional Candidates in Genome‐Wide Association Studies
Author(s) -
BulikSullivan Brendan,
Selitsky Sara,
Sethupathy Praveen
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22337
Subject(s) - biology , genome wide association study , computational biology , genetics , expression quantitative trait loci , genetic association , gene , enhancer , microrna , genome , single nucleotide polymorphism , gene expression , genotype
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. micro RNA s (mi RNA s) 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 mi RNA regulome is likely an important contributor to phenotypic variation in the human population. However, the extent to which polymorphic mi RNA ‐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 mi RNA regulome as functional candidates in GWAS . We highlight specific findings, including a variant in the promoter of the mi RNA 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 mi RNA regulome in their disease/trait of interest.