There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Paul Valdmanis |
| Institution: | University of Washington |
| Department: | Medicine |
| Country: | |
| Proposed Analysis: | Alternative splicing patterns are notoriously complex and diverse in the brain. Moreover, appropriate regulation of brain-specific splicing is lost during normal aging, which can be exacerbated by trauma or oxidative stress. We have evaluated RNA sequencing data from brain samples from patients with Alzheimer’s disease (AD) and age-matched controls. Our analysis has revealed several alternative splice products and intronic repeat sequences that are enriched in patients with AD in genes implicated in disease (APP, PSEN1 and PSEN2). Our primary objective is to integrate our RNA sequencing results with whole genome sequence data to identify intronic variants that in combination with alternative splicing products may predispose to AD. We will study AD cases and controls to identify a rare variant burden analysis across defined genomic regions. Our analysis plan is as follows: we will extract genomic regions corresponding to intronic regions that can influence alternative splicing from CRAM files. We will quantify the presence of small insertions, deletions and variants in cases and controls and use splicing prediction software to identify the potential contribution to disease. We will determine the burden of these nucleotide changes in cases, controls and large sequencing databases (e.g. gnomAD) and perform t-tests and Chi-square tests to quantify whether an enrichment of intronic variants are present in patients with AD. |
| Additional Investigators |
