Outi Quinn

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.

Abstract The genetic architecture of Multiple Sclerosis (MS) susceptibility has been extensively assessed in populations of European ancestry. Greater ancestral diversity in genetic analyses of MS susceptibility is needed to improve the utility of Multiple Sclerosis genetic risk scores, fine map causal variants underlying established associations, and thereby enhance the identification of drug targets. Here we report findings from a genetic study of Multiple Sclerosis susceptibility in an ancestrally-diverse United Kingdom-based cohort. Participants with Multiple Sclerosis were recruited via clinical sites, an online platform, and through the United Kingdom Multiple Sclerosis Register. Phenotype data were gathered using a standardised questionnaire. DNA was extracted from saliva samples obtained remotely or in person, and participants were genotyped using a commercial genotyping array. Following imputation, cases were combined with controls from the United Kingdom Biobank and subjected to stringent quality control and genetic ancestry inference. We defined two broad ancestral groups of South Asian and African ancestry. We performed within-ancestry case-control genome-wide association studies of Multiple Sclerosis susceptibility using logistic models accounting for population structure and sex. We examined both single nucleotide variants and imputed classical Human Leukocyte Antigen alleles. We curated two ancestrally-matched case-control genetic datasets (South Asian ancestry: N Case =175, N Control =6744; African ancestry: N Case =113, N Control =5177). In both ancestries, we found genetic variants within the Major Histocompatibility Complex associated with Multiple Sclerosis susceptibility (South Asian ancestry: lead variant chr6:32600515:G:A on hg38 co-ordinates, Odds Ratio=1.84, nearest gene HLA-DRB1 , P= 4.6×10 −6 ; African ancestry: lead variant chr6:29919337:A:G, Odds Ratio=2.24, nearest gene HLA-A P= 4.3×10 −5 ). European-ancestry susceptibility alleles were over-represented in cases from both ancestries, with the degree of concordance stronger for the South Asian (ρ=0.31, P =8.1×10 −6 ) than African (ρ=0.1, P =0.3) ancestry cohort. European-derived genetic risk scores performed better than chance but less well than in European ancestry cohorts, explaining 1.6% (South Asian , P =1.0×10 −4 ) and 0.5% (African , P =0.08) of the liability to MS. The genetic architecture of MS susceptibility shows strong concordance across ancestral groups suggesting shared disease mechanisms. Larger studies in diverse populations are likely to enhance our understanding of how genetic variation contributes to MS susceptibility in people of all ancestral backgrounds.

BACKGROUND AND OBJECTIVES: The genetic basis of multiple sclerosis (MS) susceptibility has been studied extensively in European (EUR) ancestry populations. The aim of our study was to determine the genetic architecture of MS susceptibility in people of South Asian (SAS) and African (AFR) genetic ancestral backgrounds. METHODS: We recruited and genotyped a cohort of ancestrally diverse people with MS (pwMS) from across the United Kingdom. Cases were combined with controls from the UK Biobank (UKB). After genetic ancestry inference, we performed within-ancestry case-control genetic association studies of MS susceptibility, exploring single nucleotide variants and imputed classical human leukocyte antigen alleles. RESULTS: allele in the SAS cohort, which has not been previously described. DISCUSSION: The genetic architecture of MS susceptibility shows strong concordance across ancestral groups suggesting shared disease mechanisms. Larger studies in diverse populations are likely to enhance our understanding of how genetic variation contributes to MS susceptibility in people of all ancestral backgrounds.

Abstract Aim Visible haematuria (VH) is a common finding on the urology ward. The high frequency of catheter blockages by clots presents a burden due to the need for bladder washes and irrigation. The pump-ball catheter drainage bag (PBCB) is designed to allow using a hand pump to dislodge blood clots through suctioning a closed system. The aim of the study was to assess the effectiveness of this device for patients with VH. Secondarily, to assess the cost effectiveness and environmental impact of the PBCB. Method A mixed quantitative and qualitative approach. In the qualitative arm, effectiveness was assessed through an anonymous questionnaire circulated to the urology multidisciplinary team. For the quantitative arm, a control group who used the standard urine bag and an intervention group who used the PBCB were identified. Data was accumulated retrospectively and prospectively from Electronic Patient Records, then compared statistically. Results The questionnaire received 26 responses. Overall, suggesting that the PBCB was faster when dislodging clots and helped to avoid bladder washouts. Of the 63 patients admitted with haematuria, 38 patients were taken as control, and 25 used the PBCB. The average number of bladder washouts decreased in the PBCB cohort when compared to the control, 1.68 and 2.28 respectively, which was statistically significant using chi-squared (p=0.011). We demonstrated an average saving of £3.38 per patient per inpatient stay using the PBCB. Conclusions Overall, the PBCB is a quick and effective tool to manage catheter blockages in patients with VH. It also reduces costs and has a beneficial environmental profile.