Genetic and non-genetic factors are closely intertwined in determining the complex pathogenetic puzzle involved in Multiple Sclerosis (MS) onset and progression.
Furthermore, literature connected biochemical markers of inflammation (e.g., C-reactive proteins, interleukins and chemokines) with MS and these in turns could be also linked to lifestyle habits, environmental factors, and genetic background.
Analyzing UK biobank offers the benefits of a large size database with high-quality measures and longitudinal assessment of outcome.
Our research will provide insights on the association between non-genetic and genetic factors and their possible interactions and MS.
Specifically, we will investigate the following aspects:
1) Is lifestyle, determined through validated questionnaires, related to the incidence and/or hazard risk of MS onset and progression, given MS status and progression may be heavily influenced by modifiable lifestyle factors?
2) Is the relationship between lifestyle and MS mediated by selected biomarkers involved in inflammation? The rationale behind this question is to better understand the pathway connecting lifestyle and MS and to quantify the effect mediated by selected MS-related biomarkers.
3) Is the relationship between genotype and MS mediated by biomarkers and lifestyle factors? The rationale is to deeply understand the connection between genotype, biomarkers and lifestyle in the risk of MS and to estimate the proportion of genotype effects mediated by non-genetic factors.
4) Are early life, environmental/ecological exposures and/or previous infection diseases related to the incidence and/or hazard risk of MS onset? And are these effects mediated by lifestyle and selected biomarkers? In this way we aim to complete the picture by also investigating the effect of these additional non-genetic factors on MS onset and progression and to estimate the proportion of non-genetic effects mediated by them.
5) Is the genotype associated with time to MS onset? The rationale is to highlight if a genetic predisposition drawing from a polygenic risk score could accelerate or delay disease onset and progression.
6) Is the interaction between genotype and non-genetic factors associated with time to MS onset? In this way we investigate if there is a different effect of genetics based on the different non-genetic factors.
As for the public health impact, this project could help identify vulnerable people, from both non-genetic characteristics and genetic background, who would benefit from targeted support and could help to direct towards preventive strategies as for the modifiable risk factors, that is encouraging healthy lifestyle behaviors. This project will take 3 years.