Approved research

A genomewide association study of autoimmunity

Lay summary

Autoimmune diseases, such as multiple sclerosis, type 1 diabetes, coeliac disease, rheumatoid arthritis, lupus and thyroid disease, are common health problems in the UK. Comparing and contrasting the results from disease specific GenomeWide Association Studies (GWAS) has shown that there are common aetiological mechanisms underlying these diseases and in this context we are proposing to undertake a GWAS with autoimmunity as the primary endpoint using genotype data from the UK Biobank as controls. Each disease specific group in this collaborative application has genotype data from many thousands of affected UK individuals. Imputation will enable us to compare these existing data with UK Biobank subjects. To supplement these already extensive existing data we will be applying for funding to undertake genotyping of the UK Biobank chip in several thousand previously untested cases. This GWAS would be well powered to identify even low frequency risk variants. The results generated might provide invaluable insight into aetiology and thereby enhance the potential development of safe, effective, rational therapies. The main analysis would exclude those participants with self-reported autoimmune disease at baseline. Further analyses would be done using self-reported cases and controls from UK Biobank in combination with data from other studies. Disease specific analysis will also be performed with similar treatment of the relevant self reported cases. It is anticipated that most if not all of the untyped UK autoimmune disease patients are not currently part of UK Biobank. Full Cohort.

Scope extension:

Autoimmune diseases, such as multiple sclerosis, type 1 diabetes, coeliac disease, rheumatoid arthritis, lupus and thyroid disease, are common health problems in the UK. Comparing and contrasting the results from disease specific GenomeWide Association Studies (GWAS) has shown that there are common aetiological mechanisms underlying these diseases and in this context we are proposing to undertake a GWAS with autoimmunity as the primary endpoint using genotype data from the UK Biobank as controls. Each disease specific group in this collaborative application has genotype data from many thousands of affected UK individuals. Imputation will enable us to compare these existing data.

We wish to extend our analysis to incude neurodegenerative conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD) and motor neurone disease (MND). Using the WGS data we will be able to identify biobank subjects carrying variants that are known to cause neurodegenerative conditions (such as those described in PMID: 31810826, 30925302, 33341150 and 24385136) and we will then be able to compare the MRI, clinical and cognitive features of those with and without these variants. Many of the variants relevant to neurodegeneration have variable penetrance and cause a range of phenotypes (PMID: 24493408).