Differential expression analysis of miRNAs expressed in blood and CSF of Huntington's disease [miRNA-seq]

Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder caused by the CAG expansion in the Huntingtin (HTT) gene. Several studies have shown the potential of microRNAs as biomarkers in neurodegenerative diseases. However, no bona fide microRNAs have been identified as promising diagnostic biomarkers for HD. As part of the PREDICT-HD project, here we performed NanoString on blood samples of 115 pre-manifest HD cases and 111 controls in an effort to provide promising biomarkers for the diagnostic of HD or the disease processes tracking. The results showed that five miRNAs (miR-1252, miR-433, miR-553, miR-138-5p and miR-2053) are significantly differentially expressed in pre-manifest gene-positive HD cases vs. gene-negative controls. We also explored the miRNAs associated with HD severity by correlating the miRNA expression with CAP scores of 115 pre-manifest HD samples and found that 41 and 24 miRNAs are negatively and positively correlated with CAP scores significantly. Furthermore, target gene set of miR-138 and miR-433 , its co-expressed mRNAs in ROSMAP, and differentially expressed mRNAs of HD reveal four overlap genes (CASP7, CNOT6L, TMED and FERMT2). In summary, our study provides new insights into biomarker of Huntington’s disease by analyzing the cross-sectional miRNA expression data in blood. In this study, total RNAs for 136 CSF samples, incl. 21 controls and 115 HD, were requested from PREDICT-HD consortium. We then sequenced the miRNA using Illumina TruSeq kit. After mapping and quantifying the miRNA normalized expression level, we called differential expressed miRNAs between control and HD using SVA, after ajusting the covariates.