Abstract
The role of microRNAs (miRNAs) in the pathogenesis of Alzheimer's disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from 3 AD genome-wide association studies (GWASs). Association with miRNA expression was tested by expression quantitative trait locus analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines. Although, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type, we highlight 2 notable outliers, that is, miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite 2 exceptions, our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA expression quantitative trait loci.
| Original language | English |
|---|---|
| Journal | Neurobiology of Aging |
| Volume | 86 |
| Pages (from-to) | 202.e1-202.e3 |
| ISSN | 0197-4580 |
| DOIs | |
| Publication status | Published - 02.2020 |
Funding
Computational support was provided by the OMICS compute cluster at the University of Lübeck. The authors thank Dr. Chun for help with JLIM, Dr. Gusev for help with TWAS/FUSION, and Dr. Lill for advice on implementing the ADmiReQTL workflow. Funding was provided by Peter und Traudl Engelhorn Foundation (to IW), by the European Medical Information Framework–Alzheimer’s Disease (EMIF-AD) [grant number 115372 ] (to LB), and by the Deutsche Forschungsgemeinschaft (DFG) [grant number BE2287/8 - 391523883 ] (to LB). Appendix A
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
