Over the past two decades there has been an explosion in genetic research, primarily due to advances in molecular genetic technologies, starting from studies of single genetic variants, candidate genes, and biological pathways, moving on to array-based genome-wide association studies (GWAS), and subsequently to next generation sequencing (NGS).
These studies have contributed with important knowledge regarding the significance of sequence variation in relation to age-related traits and diseases. However, the genetic variants consistently identified for different traits account for only a small part of the estimated heritability.
To face this challenge of “missing heritability”, researchers have looked for new and innovative approaches to identify determinants of human aging and its affiliated diseases. This has resulted to an increased interest in functional genomic studies, such as studies of the epigenome (regulation and control of gene expression), the transcriptome (gene expression), the proteome (gene products), and the metabolome (complete set of metabolites within biological sample), which potentially can lead to the identification of molecular markers accounting for a significant fraction of the “missing heritability”.
Purpose
The purpose of the project is to apply the powerful discordant monozygotic twin design to investigate the contribution of epigenetic, transcriptomic, and proteomic signatures in the development of cardiovascular disease (CVD) with focus on coronary artery diseases (CAD) (ICD10 codes: I20-I25) in twins holding each omics.
We both want to develop novel twin designs and apply state-of-the-art statistical multi-omics methods related to for instance integrative network analysis, similarity networks, artificial intelligence, and neural networks.
Material
The study population comprise 835 twins drawn from three population-based and nation-wide surveys from the Danish Twin Registry: The Longitudinal Study of Aging Danish Twins, The Middle Age Danish Twin study, and the Birthweight-Discordant Study. Survival status was retrieved from the Danish Central Person Register and information on diagnoses of CVD obtained for the same individuals from the Danish National Patient Registry. Biological data were based on blood samples.
Funding
- Fabrikant Vilhelm Pedersen and Hustrus Mindelegat on recommendation by the Novo Nordisk Foundation
- Aase and Ejnar Danielsen's Foundation
- Else and Mogens Wedell Wedellsborgs Foundation
- Ulla and Mogens Folmer Andersens Foundation
- Danish Council for Independent Research—Medical Sciences (DFF- 6110-00016)
- European Union’s Seventh Framework Programme (FP7/2007–2011) under grant Agreement No. 259679
- National Program for Research Infrastructure 2007 grant 09-063256 from the Danish Agency, for Science Technology and Innovation.
Main Supervisor:
- Mette Soerensen Thinggaard, University of Southern Denmark
Co-supervisors:
- Hans Christian Beck, University of Southern Denmark and Odense University Hospital
- Qihua Tan, University of Southern Denmark.