Professor V Hugh Perry is Professor of Experimental Neuropathology within Biological Sciences at the University of Southampton. He is also Chair Neuroscience and Mental Health Board. MRC, UK; Visiting Professor in the College of Medicine & Veterinary Medicine. University of Edinburgh. Hugh is a member of the UK CFS/ME Research Collaborative Executive Board and is supporting the development of MEGA.
Genome Wide Associated Studies (GWAS) studies are a key route to understanding complex diseases and how they might be treated and a GWAS is the approach that the MEGA team is working on.
An example of how GWAS has transformed other illness fields is its use with Alzheimer’s disease. There are more than 850,000 people in the UK with dementia of which the most common form is Alzheimer’s disease. The causes of Alzheimer’s disease are poorly understood, although as with many complex diseases it is believed to be an interaction between an individual’s genetic make -up and environmental factors.
It has been known for many years that a polymorphism, a small genetic difference between individuals, in the protein called ApoE, is a risk factor for Alzheimer’s disease but the contribution of other genes involved has only come to light through very large scale GWAS. Discovering the genes which may each alone have a small effect on disease requires very large numbers of samples from individuals diagnosed with the disease.
The most recent GWAS studies, now from collections of nearly 75,000 DNA samples, have produced exciting and insightful results. It appears that alterations in genes associated with cholesterol metabolism, synaptic signalling and the immune system are risk factors for developing Alzheimer’s disease. This opens new routes for diagnosis and opportunities for intervention. The unexpected involvement of the immune system, for example, suggests modulation of immune pathways both in the brain and also peripheral to the brain may impact on disease onset or progression.
To read more about this research: Cuyvers E, Sleegers K. Genetic variations underlying Alzheimer’s disease: evidence from genome-wide association studies and beyond. Lancet Neurol. 2016. Jul;15(8):857-68. Review.