JPND: BRain Imaging, cognition, Dementia and next generation GEnomics
Award Number
MR/N027558/1Programme
Research GrantStatus / Stage
ActiveDates
1 May 2016 -30 April 2019
Duration (calculated)
02 years 11 monthsFunder(s)
MRC (UKRI)Funding Amount
£480,915.76Funder/Grant study page
MRC UKRIContracted Centre
University of EdinburghContracted Centre Webpage
Principal Investigator
Professor Deary, Ian J.PI Contact
I.Deary@ed.ac.ukPI ORCID
0000-0002-1733-263XWHO Catergories
Development of BiomarkersUnderstanding Underlying Disease
Disease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 260 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Award Number | MR/N027558/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20160501 |
| End Date | 20190430 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | MRC UKRI |
| Contracted Centre | University of Edinburgh |
| Contracted Centre Webpage | |
| Funding Amount | £480,915.76 |
Abstract
We propose to explore the genetic and epigenetic determinants of quantitative MRI-markers of brain aging that are powerful predictors of dementia/AD risk, and to examine the clinical significance of the markers in a population-based setting. Leveraging the extensive information collected within the largest European population-based cohort studies with neuroimaging data, we will first search for genetic variants associated with established and novel MRI-markers of brain aging, focusing particularly on rare variants, using both an agnostic and candidate locus approach (loci identified through genome-wide association studies [GWAS] as associated AD or with MRI-markers of brain aging). In contrast with GWAS signals, rare variants may lead to the discovery of causal variants, and have hardly been explored in association with structural MRI-markers. Second, we will take an original lifetime perspective, through examination of samples in various age categories spanning from young adulthood to older age, many of which with repeated MRI and blood sampling. Indeed, there is increasing evidence that early-life factors play an important role in the occurrence of late-onset neurodegenerative diseases. We propose an innovative exploration of lifetime changes in methylation associated with structural brain alterations using a novel bisulfite sequencing technology, to help identify functional and disease relevant variants. We will also study the modifying effect of vascular risk factors and socio-economic status on genetic/epigenetic determinants of brain aging. Third, we will explore the clinical significance of genetic and epigenetic markers we identify by examining their association with cognitive performance, cognitive decline and risk of dementia/AD, capitalizing on the elaborate cognitive testing and prospective dementia surveillance available in all studies.
Aims
We propose to explore the genetic and epigenetic determinants of quantitative MRI-markers of brain aging that are powerful predictors of dementia/AD risk, and to examine the clinical significance of the markers in a population-based setting. Leveraging the extensive information collected within the largest European population-based cohort studies with neuroimaging data, we will first search for genetic variants associated with established and novel MRI-markers of brain aging, focusing particularly on rare variants, using both an agnostic and candidate locus approach (loci identified through genome-wide association studies [GWAS] as associated AD or with MRI-markers of brain aging). In contrast with GWAS signals, rare variants may lead to the discovery of causal variants, and have hardly been explored in association with structural MRI-markers. Second, we will take an original lifetime perspective, through examination of samples in various age categories spanning from young adulthood to older age, many of which with repeated MRI and blood sampling. Indeed, there is increasing evidence that early-life factors play an important role in the occurrence of late-onset neurodegenerative diseases. We propose an innovative exploration of lifetime changes in methylation associated with structural brain alterations using a novel bisulfite sequencing technology, to help identify functional and disease relevant variants. We will also study the modifying effect of vascular risk factors and socio-economic status on genetic/epigenetic determinants of brain aging. Third, we will explore the clinical significance of genetic and epigenetic markers we identify by examining their association with cognitive performance, cognitive decline and risk of dementia/AD, capitalizing on the elaborate cognitive testing and prospective dementia surveillance available in all studies.