Project: HD-READy (High-Dimensional Research in Alzheimer’s Disease)
Genetics and brain imaging are two important omics-technologies in research on neurodegenerative diseases (ND), and have undergone tremendous technological development in recent years. In coming years, combining imaging and genetics into joint analysis holds great promise to further unlock the etiology of neurodegenerative disease. However, analytical methodology and infrastructure that address such ultra-high-dimensional data are lacking. By bringing together several large longitudinal cohort studies with imaging genetics data, this working group aims to tackle issues related to ultra-high-dimensional omics-data.
Specifically, two research needs will be addressed:
1) Analytical methodology for ultra-high-dimensional data. Conventional strategies for joint analysis, i.e. individual-level pooling versus study-level meta-analysis, have several disadvantages related to legal, ethical, and logistic constraints. This working aims to develop a meta-analytical approach, which 1) provides effect estimates that are equivalent to individual-level meta-analysis; 2) can be shared without disclosing identifiable participant information; 3) is easily applied to large neuroimaging and genetic datasets. 2) Infrastructure to facilitate analysis of ultra-high-dimensional data. The working group will provide recommendations for harmonization of imaging genetics data. Additionally, the working group will provide recommendations regarding possible solutions for sufficient computational infrastructure, which may include cloud computing and access to central computing clusters, whilst
complying with constraints mentioned in aim 1. This Working Group brings together 23 collaborators from 15 population-based longitudinal cohort studies from 6 EU and 2 non-EU countries. Furthermore, an international Advisory Reference Group will be formed, which consists of key members from other large consortia, including ENIGMA, International Stroke Genetics Consortium, ADGC and IGAP. The working group will hold bi-weekly teleconferences and meet in-person twice during the course of this grant. Ultimately, recommendations will be disseminated in manuscripts, conference presentations, and presentations during consortium meetings.
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