MRI case studies

Organ fibrosis accounts for an estimated one-third of all deaths worldwide. It is associated with ageing and metabolic abnormalities that occur in response to a range of known and unknown genetic and environmental factors.

Understanding shared pathogenic mechanisms, especially in early disease, may identify shared clusters of disease that will respond to lifestyle modification or repurposing of available therapies.

Common genetic, environmental, lifestyle and socioeconomic factors, or biological pathways that link these mechanistic clusters aren’t readily recognised by conventional disease and organ centred approaches. Focusing on the mechanistic basis of a biological process such as fibrosis offers a unique opportunity to recognise early disease, identify disrupted mechanisms and repurpose drugs that have a disease-specific indication to target the underlying pathological process.

The association of brain neuroimaging-derived features with fibrosis genetic risk

Organ fibrosis is associated with impaired brain function (e.g. cognitive decline), accelerated brain ageing, and increased risk of neurodegenerative disorders and cerebrovascular accidents. This may be related to direct brain injury from shared risk factors manifesting as neuroinflammation, microgliosis and accelerated vascular ageing or indirectly due to organ dysfunction affecting brain health (e.g. acute or chronic hepatic, diabetic or renal encephalopathy).

To disentangle these mechanisms, our BRC has used the UK Biobank combined imaging, genetic, and clinical data to undertake brain-wide and hypothesis-driven region-specific association studies of known fibrosis genetic risk factors, explore association signals with gene expression brain atlases to differentiate direct from indirect effects, and assess mediating and moderator effects from lifestyle, clinical, physiological, and imaging fibrosis markers.

About the graphic: This is a Manhattan plot of the brain-wide association study outcomes of 17 known idiopathic pulmonary fibrosis (IPF) variants using UK Biobank imaging cohort (S=32,431). Each of the IPF variants is coded by a different colour and within each of these colour groups, associations with the 1,248 brain imaging features are depicted.