. 2023 May 17;13(5):e071656.

doi: 10.1136/bmjopen-2023-071656.

ADAMS project: a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the UK

Benjamin M Jacobs¹, Luisa Schalk¹, Angie Dunne², Antonio Scalfari³, Ashwini Nandoskar⁴, Bruno Gran⁵, Charles A Mein⁶, Charlotte Sellers¹, Cord Spilker⁷, David Rog⁸, Elisa Visentin⁹, Elizabeth Lindsey Bezzina¹⁰, Emeka Uzochukwu¹¹, Emma Tallantyre^{11

12}, Eva Wozniak⁶, Eve Sacre², Ghaniah Hassan-Smith¹³, Helen L Ford², Jade Harris¹⁴, Joan Bradley¹⁵, Joshua Breedon¹, Judith Brooke¹⁴, Karim L Kreft¹⁶, Katherine Tuite Dalton¹⁷, Katila George¹, Maria Papachatzaki¹⁸, Martin O'Malley², Michelle Peter¹, Miriam Mattoscio¹⁹, Neisha Rhule²⁰, Nikos Evangelou²¹, Nimisha Vinod¹⁴, Outi Quinn⁷, Ramya Shamji⁹, Rashmi Kaimal¹, Rebecca Boulton²¹, Riffat Tanveer²², Rod Middleton¹⁷, Roxanne Murray¹, Ruth Bellfield⁷, Sadid Hoque¹, Shakeelah Patel²², Sonia Raj²², Stephanie Gumus¹⁸, Stephanie Mitchell¹⁴, Stephen Sawcer²³, Tarunya Arun²⁴, Tatiana Pogreban⁹, Terri-Louise Brown¹, Thamanna Begum¹, Veronica Antoine¹⁴, Waqar Rashid²⁵, Alastair J Noyce¹, Eli Silber¹⁰, Huw Morris²⁶, Gavin Giovannoni¹, Ruth Dobson²⁷

Affiliations

¹ Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
² Leeds Centre for Neurosciences, Leeds teaching Hospitals NHS Trust, Leeds, UK.
³ Centre of Neuroscience, Department of Medicine, Imperial College London, London, UK.
⁴ Hillingdon and Imperial NHS Trust, London, UK.
⁵ Department of Neurology, Nottingham University Hospitals NHS Trust, Mental Health and Clinical Neuroscience Academic Unit, University of Nottingham School of Medicine, Nottingham, UK.
⁶ Barts and the London Genome Centre, Queen Mary University of London, London, UK.
⁷ Bradford Teaching Hospital Foundation Trust, Bradford, UK.
⁸ Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Trust, Manchester, UK.
⁹ Research and Innovation, Queen's Hospital, BHRUT, London, UK.
¹⁰ Kings College Hospital and Lewisham and Greenwich NHS Trusts, London, UK.
¹¹ Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
¹² Department of Clinical Neurology, University Hospital of Wales, Cardiff, UK.
¹³ University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹⁴ Northern Care Alliance NHS Trust, Manchester, UK.
¹⁵ Hillingdon and Imperial NHS Trust, Uxbridge, UK.
¹⁶ Department of Neurology, University Hospital of Wales, Cardiff, UK.
¹⁷ Population Data Science, Swansea University Medical School, Swansea, UK.
¹⁸ Mid and South Essex NHS Foundation Trust, Southend-on-Sea, UK.
¹⁹ Department of neuroscience, Queen's Hospital, BHRUT NHS Trust, Romford, UK.
²⁰ Queen Elizabeth Hospital (Lewisham and Greenwich NHS Trust), London, UK.
²¹ Department of Neurology, Nottingham University Hospitals NHS Trust; Mental Health and Clinical Neuroscience Academic Unit, University of Nottingham School of Medicine, Nottingham, UK.
²² Lancashire Teaching Hospital NHS Foundation Trust, Preston, UK.
²³ University of Cambridge, Department of Clinical Neuroscience, Addenbrookes Hospital, Hills Road, Cambridge, UK.
²⁴ University Hospitals of Coventry and Warwickshire, Coventry, UK.
²⁵ St George's University Hospitals NHS Foundation Trust, London, UK.
²⁶ Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, London, UK.
²⁷ Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, London, UK ruth.dobson@qmul.ac.uk.

PMID: 37197821
PMCID: PMC10193065
DOI: 10.1136/bmjopen-2023-071656

ADAMS project: a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the UK

Benjamin M Jacobs et al. BMJ Open. 2023.

. 2023 May 17;13(5):e071656.

doi: 10.1136/bmjopen-2023-071656.

Authors

Affiliations

¹ Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
² Leeds Centre for Neurosciences, Leeds teaching Hospitals NHS Trust, Leeds, UK.
³ Centre of Neuroscience, Department of Medicine, Imperial College London, London, UK.
⁴ Hillingdon and Imperial NHS Trust, London, UK.
⁵ Department of Neurology, Nottingham University Hospitals NHS Trust, Mental Health and Clinical Neuroscience Academic Unit, University of Nottingham School of Medicine, Nottingham, UK.
⁶ Barts and the London Genome Centre, Queen Mary University of London, London, UK.
⁷ Bradford Teaching Hospital Foundation Trust, Bradford, UK.
⁸ Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Trust, Manchester, UK.
⁹ Research and Innovation, Queen's Hospital, BHRUT, London, UK.
¹⁰ Kings College Hospital and Lewisham and Greenwich NHS Trusts, London, UK.
¹¹ Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
¹² Department of Clinical Neurology, University Hospital of Wales, Cardiff, UK.
¹³ University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹⁴ Northern Care Alliance NHS Trust, Manchester, UK.
¹⁵ Hillingdon and Imperial NHS Trust, Uxbridge, UK.
¹⁶ Department of Neurology, University Hospital of Wales, Cardiff, UK.
¹⁷ Population Data Science, Swansea University Medical School, Swansea, UK.
¹⁸ Mid and South Essex NHS Foundation Trust, Southend-on-Sea, UK.
¹⁹ Department of neuroscience, Queen's Hospital, BHRUT NHS Trust, Romford, UK.
²⁰ Queen Elizabeth Hospital (Lewisham and Greenwich NHS Trust), London, UK.
²¹ Department of Neurology, Nottingham University Hospitals NHS Trust; Mental Health and Clinical Neuroscience Academic Unit, University of Nottingham School of Medicine, Nottingham, UK.
²² Lancashire Teaching Hospital NHS Foundation Trust, Preston, UK.
²³ University of Cambridge, Department of Clinical Neuroscience, Addenbrookes Hospital, Hills Road, Cambridge, UK.
²⁴ University Hospitals of Coventry and Warwickshire, Coventry, UK.
²⁵ St George's University Hospitals NHS Foundation Trust, London, UK.
²⁶ Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, London, UK.
²⁷ Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, London, UK ruth.dobson@qmul.ac.uk.

PMID: 37197821
PMCID: PMC10193065
DOI: 10.1136/bmjopen-2023-071656

Abstract

Purpose: Genetic studies of multiple sclerosis (MS) susceptibility and severity have focused on populations of European ancestry. Studying MS genetics in other ancestral groups is necessary to determine the generalisability of these findings. The genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis (ADAMS) project aims to gather genetic and phenotypic data on a large cohort of ancestrally-diverse individuals with MS living in the UK.

Participants: Adults with self-reported MS from diverse ancestral backgrounds. Recruitment is via clinical sites, online (https://app.mantal.co.uk/adams) or the UK MS Register. We are collecting demographic and phenotypic data using a baseline questionnaire and subsequent healthcare record linkage. We are collecting DNA from participants using saliva kits (Oragene-600) and genotyping using the Illumina Global Screening Array V.3.

Findings to date: As of 3 January 2023, we have recruited 682 participants (n=446 online, n=55 via sites, n=181 via the UK MS Register). Of this initial cohort, 71.2% of participants are female, with a median age of 44.9 years at recruitment. Over 60% of the cohort are non-white British, with 23.5% identifying as Asian or Asian British, 16.2% as Black, African, Caribbean or Black British and 20.9% identifying as having mixed or other backgrounds. The median age at first symptom is 28 years, and median age at diagnosis is 32 years. 76.8% have relapsing-remitting MS, and 13.5% have secondary progressive MS.

Future plans: Recruitment will continue over the next 10 years. Genotyping and genetic data quality control are ongoing. Within the next 3 years, we aim to perform initial genetic analyses of susceptibility and severity with a view to replicating the findings from European-ancestry studies. In the long term, genetic data will be combined with other datasets to further cross-ancestry genetic discoveries.

Keywords: GENETICS; Multiple sclerosis; Neurology.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

References

1. International multiple sclerosis genetics Consortium (IMSGC) et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 2013;45:1353–60. 10.1038/ng.2770 - DOI - PMC - PubMed
1. International Multiple Sclerosis Genetics Consortium . Multiple sclerosis genomic MAP implicates peripheral immune cells and microglia in susceptibility. Science 2019;365:eaav7188. 10.1126/science.aav7188 - DOI - PMC - PubMed
1. Sawcer S, Ban M, Maranian M, et al. A high-density screen for linkage in multiple sclerosis. Am J Hum Genet 2005;77:454–67. 10.1086/444547 - DOI - PMC - PubMed
1. International Multiple Sclerosis Genetics Consortium . Low-Frequency and rare-coding variation contributes to multiple sclerosis risk. Cell 2019;178:262. - PMC - PubMed
1. Sawcer S, Hellenthal G, Pirinen M, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476:214–9. 10.1038/nature10251 - DOI - PMC - PubMed

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ADAMS project: a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the UK

Affiliations

ADAMS project: a genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis based in the UK

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials