B3571 - Genomic determinants of Multiple Sclerosis susceptibility in an ethnically diverse population - 19/08/2020

B number: 
B3571
Principal applicant name: 
Benjamin Meir Jacobs | Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London (United Kingdom)
Co-applicants: 
Dr Ruth Dobson, Professor Huw Morris
Title of project: 
Genomic determinants of Multiple Sclerosis susceptibility in an ethnically diverse population
Proposal summary: 

Multiple Sclerosis (MS) is a disorder of the brain and spinal cord which affects about 1 in 1000 people worldwide. In people with MS (pwMS), the immune system attacks the lining of nerve (myelin), leading to ‘attacks’ of disability which can last days-months, and a gradual accumulation of disability over time. Although there are many effective treatments for MS, there is still no cure. MS was previously thought to mainly affect White people, but recent evidence suggests this is untrue: in the USA, the number of newly-diagnosed people with MS is now higher among African American individuals than individuals of White European ancestry.

Most of our understanding of what causes MS comes from studies of European individuals. The largest genetic association study to date revealed over 200 sites in the genome associated with MS, but it remains unclear whether these insights - from an exclusively European cohort - apply to individuals from different ethnic backgrounds.

In this study, we attempt to perform the largest genetic association study of MS among Black, Asian, and Minority Ethnic (BAME) individuals to date in the UK. We will collect genetic data from people with MS and healthy controls from BAME backgrounds, and we will systematically search for genetic variants more common in the pwMS. We anticipate that this research will advance our understanding of what causes MS in BAME individuals, and may have important implications for our understanding of the causes of MS more broadly.

Impact of research: 
For the scientific community Develop greater understanding of how established MS risk alleles differ in their effect sizes between different populations Develop greater understanding of how ‘novel’ risk alleles contribute to MS susceptibility in ethnic minority populations Leverage association signals from individuals of African ancestry to improve fine-mapping at MS risk loci (exploiting the more granular LD structure) Use ancestry-specific genetic associations to develop ancestry-specific, and ‘pan-ancestral’ polygenic risk scores for causal inference, studies of gene-environment interaction, disease prediction Use ancestry-specific associations to predict novel drug targets, and develop hypotheses for rational pharmacogenomic drug design. Develop and improve tools for ancestry inference and integrating genetic data from ethnically diverse datasets. For people with MS Ensure people with MS from ethnic minorities feel represented in the research environment Re-educate the public, the scientific community, and the clinical community on the perception that MS is a disease of White European individuals only, which it clearly is not Strive towards rational and equitable drug development, ensuring that individuals who have been represented less in GWAS benefit equally from advances in disease-modifying therapies For society at large Improve the visibility of people from ethnic minority backgrounds in genetic research As a consequence of the above, ensure that individuals from ethnic minority backgrounds benefit equally from the wide range of medical advances spawned by genetic research
Date proposal received: 
Friday, 17 July, 2020
Date proposal approved: 
Monday, 20 July, 2020
Keywords: 
Neurology, Multiple sclerosis, Gene mapping, GWAS, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Genetic epidemiology, Genetics, Genomics, Genome wide association study, Immunity, Statistical methods