| Title: | Molecular underpinnings of resting-state fMRI |
| Lead Institution: | Stanford University |
| Principal investigator: | Dr Michael Greicius |
Application 45420
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About
Our project has two main goals: (i) identify genes and causal genetic variants that regulates the variance of resting-state fMRI phenotypes; (ii) develop multivariate approaches taking into account the potential joint effects between genes and/or covariations between brain regions. Resting-state fMRI leverages the fact that even at rest the brain remains functionally active. In this passive state, every brain region shows ongoing low-frequency fluctuations of neural activity that can be detected with fMRI. Critically, these low-frequency fluctuations are strongly temporally correlated across brain regions. Measures of temporal correlation between two brain regions are used to define functional connectivity and, when applied across several brain regions are used to define resting-state networks (RSNs). Recent imaging genetic studies have emphasized the heritability of resting-state fMRI associated phenotypes. Our aim is to go a step further and identify the underlying genetic variants which regulate these phenotypes. The functional connectivity within RSNs has been shown to discriminate controls and people with brain disorders. Our study will enable to understand the molecular mechanisms at stake in the RSNs variability across individuals. This meets the UK Biobank's stated purpose because characterizing the genes that regulates the resting-state phenotypes will contribute to build a reference set of genes the variability in the general population. This will in turn help to better identify and understand the potential genetic patterns underlying diseases for which the variability in RSNs has been shown to be a biomarker, such as the default mode network which distinguishes Alzheimer's disease from healthy aging.2 Publications
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 12320 | Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease | Yann Le Guen (+109) | 2022 | JAMA Neurology |
| 9924 | Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer's disease | Prabesh Bhattarai (+29) | 2024 | Acta Neuropathologica |
Enabling scientific discoveries that improve human health