Project: Defining Genetic, Polygenic and Environmental Risk for Alzheimer's Disease using multiple powerful cohorts, focussed Epigenetics and Stem cell metabolomics
Through the pooling of our existing resources and novel analytical biostatistical/informatics methods, we will identify several new susceptibility genes for Alzheimer’s disease (AD), produce the most comprehensive estimates of AD genetic risk available worldwide, test for G x E relationships in the largest sample of epidemiological cohorts collaborating to date and undertake focussed studies taking genetics and environmental findings into novel areas of research, using metabolomics, epigenetics and reprogrammed induced pluripotent stem cells (iPSC). We will pool our (i) SNP GWAS and replication data; (ii) exome chip GWAS data; iii) whole exome sequencing data; iv) re-imputation and analyses of all GWAS; (v) targeted resequencing and replication genotyping. We will use these powerful resources to construct novel polygenic scores to define levels of AD risk both overall and within functional pathways implicated. We will take these polygenic score analyses and identify those at greatest and least risk of AD. We will study the interplay between genetic and environmental risk factors in our collection of epidemiological cohorts. We will use biomarker data and characterise these individuals to understand triggers leading to AD. Finally, we will undertake focussed studies of iPSC metabolomics, testing methylation changes on AD risk loci in those at high and low AD genetic risk to improve our understanding of the factors that trigger AD.
| Acronym | PERADES (Reference Number: JPND_RF-542-008) |
| Duration | 01/01/2014 - 01/01/2017 |
| Project Topic | Neurodegenerative disease |
| Website | visit project website |
| Network | JPND |
| Call | A JPND call for European research projects for the identification of genetic, epigenetic and environmental risk and protective factors for Neurodegenerative Diseases |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Cardiff University | Coordinator | United Kingdom |
| 2 | Erasmus Medical Centre | Partner | Netherlands |
| 3 | INSERM U744 | Partner | France |
| 4 | INSERM U614 | Partner | France |
| 5 | VU University Medical Centre | Partner | Netherlands |