B4390 - Explore genetic epigenetic and metabolomic associations with longitudinal muscle strength physical fitness and mental health - 17/04/2024

B number: 
B4390
Principal applicant name: 
Yunfeng Huang | Biogen
Co-applicants: 
Dr. Ellen Tsai, Dr. Chia-Yen Chen, Denis Baird
Title of project: 
Explore genetic, epigenetic and metabolomic associations with longitudinal muscle strength, physical fitness and mental health
Proposal summary: 

Muscle strength and cognitive function are partially driven by genes inherited from parents. Reduction in muscle strength and cognitive function is associated with multiple adverse health outcomes including disability and mortality. Previous studies identified genes commonly associated with muscle strength and cognitive performance. However, impacts of genetic determinants of muscle strength and cognitive function on physical fitness and mental health longitudinally have not been fully studied mainly due to data unavailability. ALSPAC (Avon Longitudinal Study of Parents and Children) has collected physical fitness (hand grip strength, body DXA scan) and mental health (depression, anxiety, life events, etc.) data from mothers and children longitudinally, along with genetic data. Our aim is to leverage this dataset to better understand how genetic predispositions to muscle strength and cognitive performance contribute to physical fitness and mental health over time.

Reduction in physical fitness and motor function is associated with accelerated aging reflected by changes in DNA methylation, another heritable mark that can be modified by behavioral and environmental factors. Associations of DNA methylation with longitudinal physical fitness and mental health have not been fully understood. Using data from the ALSPAC, we plan to study the longitudinal association of physical fitness and mental health with DNA methylation throughout the genome. Furthermore, we plan to evaluate the biochemical effects of genes and/or DNA methylation marks associated with longitudinal physical fitness and mental health, by studying their associations with levels of different biochemicals (called ‘metabolites’) in child and mother’s blood samples using the metabolomics data in ALSPAC.

Impact of research: 
This research will help us better understand the genetic, epigenetic, and metabolomic associations with physical fitness, muscle strength and mental health from a longitudinal perspective. Reduction in physical fitness and cognitive function is associated with multiple adverse health outcomes and has a potential link with mental illnesses. A better grasp of underlying biological mechanisms through our proposed multi-omics approach can facilitate therapeutic development for age-associated diseases.
Date proposal received: 
Thursday, 3 August, 2023
Date proposal approved: 
Monday, 14 August, 2023
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Muscle weakness, physical fitness, mental illnesses, GWAS, Metabolomics, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Epigenetics, Genetic epidemiology, Genome wide association study, Metabolic - metabolism, Physical - activity, fitness, function