microRNA相关的变异与阿尔茨海默病风险相关的全基因组鉴定.pdfVIP

/scientificreports OPEN Genome-wide identification of microRNA-related variants associated with risk of Alzheimer’s Received: 30 January 2016 disease Accepted: 03 June 2016 Published: 22 June 2016 1,2 1,3,4 5 1,6 Mohsen Ghanbari , M. Arfan Ikram , Hans W. J. de Looper , Albert Hofman , 7 1 1 Stefan J. Erkeland , Oscar H. Franco Abbas Dehghan MicroRNAs (miRNAs) serve as key post-transcriptional regulators of gene expression. Genetic variation in miRNAs and miRNA-binding sites may affect miRNA function and contribute to disease risk. Here, we investigated the extent to which variants within miRNA-related sequences could constitute a part of the functional variants involved in developing Alzheimer’s disease (AD), using the largest available genome-wide association study of AD. First, among 237 variants in miRNAs, we found rs2291418 in the miR-1229 precursor to be significantly associated with AD (p-value = 6.8 × 10−5, OR = 1.2). Our in-silico analysis and in-vitro miRNA expression experiments demonstrated that the variant’s mutant allele enhances the production of miR-1229-3p. Next, we found miR-1229-3p target genes t