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8. Type 1 Diabetes Genetic Risk Contributes to Phenotypic Presentation in Monogenic Autoimmune Diabetes.

Author

Luckett, Amber M., Hawkes, Gareth, Green, Harry D., De Franco, Elisa, Hagopian, William A., Roep, Bart O., Weedon, Michael N., Oram, Richard A., Johnson, Matthew B., Dobbs, Rebecca A, Domingo-Vila, Clara, Gillespie, Kathleen M, Hattersley, Andrew T, Hudson, Michelle, McDonald, Timothy J, Morgan, Noel G, Murrall, Kathryn, Richardson, Sarah J, Smithmyer, Megan E, and Speake, Cate

Subjects
GENETIC risk score, TYPE 1 diabetes, SINGLE nucleotide polymorphisms, MONOGENIC & polygenic inheritance (Genetics), HAPLOTYPES
Abstract

Disease-causing variants in key immune homeostasis genes can lead to monogenic autoimmune diabetes. Some individuals carrying disease-causing variants do not develop autoimmune diabetes, even though they develop another autoimmune disease. We aimed to determine whether type 1 diabetes polygenic risk contributes to phenotypic presentation in monogenic autoimmune diabetes. We used a 67 single nucleotide polymorphism type 1 diabetes genetic risk score (T1D-GRS) to determine polygenic risk in 62 individuals with monogenic autoimmune diabetes and 180 control individuals with nonautoimmune neonatal diabetes (NDM). We used population-based control participants (n = 10,405) and individuals with type 1 diabetes (n = 285) as a comparator. Individuals with monogenic autoimmune diabetes had higher T1D-GRSs compared with individuals with nonautoimmune NDM (mean 11.3 vs. 9.8; P = 1.7 × 10−5) and controls (mean 10.3; P = 7.5 × 10−6), but the levels were markedly lower than those for individuals with type 1 diabetes (14.9; P = 3.3 × 10−21). These differences were explained by individuals with monogenic autoimmune diabetes having higher class II HLA genetic risk, specifically from the DRB1* 03:01 -DQA1 *05:01 -DQB1 *02:01 haplotype (DR3-DQ2) (P < 0.01). In the presence of monogenic autoimmunity, the polygenic class II HLA susceptibility contributes to development of autoimmune diabetes. This suggests a role of class II HLA in targeting the dysregulated immune response toward the β-cell. Article Highlights: There is variability in early-onset autoimmune diabetes presentation in individuals with monogenic autoimmunity; the mechanism(s) underlying this is unclear. We examined whether type 1 diabetes (T1D) polygenic risk contributes to clinical phenotype in monogenic autoimmune diabetes. Individuals with monogenic autoimmune diabetes had higher T1D genetic risk scores compared with control cohorts, driven largely by increased presence of T1D-risk DR3-DQ2 haplotype. Established T1D polygenic risk alleles, particularly class II HLA genes, contribute to clinical presentation in monogenic autoimmunity. [ABSTRACT FROM AUTHOR]

Published
2025
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9. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study

Author

Patel, Vinod, Mazhar, Zia, Saich, Rebecca, Colleypriest, Ben, Tham, Tony C, Iqbal, Tariq H, Kaushik, Vishal, Murugesan, Senthil, Singh, Salil, Weaver, Sean, Preston, Cathryn, Butt, Assad, Smith, Melissa, Basude, Dharamveer, Beale, Amanda, Langlands, Sarah, Direkze, Natalie, Parkes, Miles, Torrente, Franco, De La Revella Negro, Juan, MacDonald, Chris Ewen, Evans, Stephen M, Gunasekera, Anton V J, Thakur, Alka, Elphick, David, Shenoy, Achuth, Nwokolo, Chuka U, Dhar, Anjan, Cole, Andrew T, Agrawal, Anurag, Bridger, Stephen, Doherty, Julie, Cooper, Sheldon C, de Silva, Shanika, Mowat, Craig, Mayhead, Phillip, Lees, Charlie, Jones, Gareth, Ahmad, Tariq, Hart, James W, Gaya, Daniel R, Russell, Richard K, Gervais, Lisa, Dunckley, Paul, Mahmood, Tariq, Banim, Paul J R, Sonwalkar, Sunil, Ghosh, Deb, Phillips, Rosemary H, Azaz, Amer, Sebastian, Shaji, Shenderey, Richard, Armstrong, Lawrence, Bell, Claire, Hariraj, Radhakrishnan, Matthews, Helen, Jafferbhoy, Hasnain, Selinger, Christian P, Zamvar, Veena, De Caestecker, John S, Willmott, Anne, Miller, Richard, Babu, Palani Sathish, Tzivinikos, Christos, Bloom, Stuart L, Chung-Faye, Guy, Croft, Nicholas M, Fell, John ME, Harbord, Marcus, Hart, Ailsa, Hope, Ben, Irving, Peter M, Lindsay, James O, Mawdsley, Joel E, McNair, Alistair, Monahan, Kevin J, Murray, Charles D, Orchard, Timothy, Paul, Thankam, Pollok, Richard, Shah, Neil, Bouri, Sonia, Johnson, Matt W, Modi, Anita, Kabiru, Kasamu Dawa, Baburajan, B K, Bhaduri, Bim, Fagbemi, Andrew Adebayo, Levison, Scott, Limdi, Jimmy K, Watts, Gill, Foley, Stephen, Ramadas, Arvind, MacFaul, George, Mansfield, John, Grellier, Leonie, Morris, Mary-Anne, Tremelling, Mark, Hawkey, Chris, Kirkham, Sian, Charlton, Charles PJ, Rodrigues, Astor, Simmons, Alison, Lewis, Stephen J, Snook, Jonathon, Tighe, Mark, Goggin, Patrick M, De Silva, Aminda N, Lal, Simon, Smith, Mark S, Panter, Simon, Cummings, J R Fraser, Dharmisari, Suranga, Carter, Martyn, Watts, David, Mahmood, Zahid, McLain, Bruce, Sen, Sandip, Pigott, Anna J, Hobday, David, Wesley, Emma, Johnston, Richard, Edwards, Cathryn, Beckly, John, Vani, Deven, Ramakrishnan, Subramaniam, Chaudhary, Rakesh, Trudgill, Nigel J, Cooney, Rachel, Bell, Andy, Prasad, Neeraj, Gordon, John N, Brookes, Matthew J, Li, Andy, Gore, Stephen, Kennedy, Nicholas A, Heap, Graham A, Green, Harry D, Hamilton, Benjamin, Bewshea, Claire, Walker, Gareth J, Thomas, Amanda, Nice, Rachel, Perry, Mandy H, Chanchlani, Neil, Heerasing, Neel M, Hendy, Peter, Lin, Simeng, Lees, Charlie W, Hart, Ailsa L, Mansfield, John C, Lindsay, James, McDonald, Timothy J, McGovern, Dermot, and Goodhand, James R

Published
2019
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10. Colorectal cancer risk stratification using a polygenic risk score in symptomatic patients presenting to primary care — a UK Biobank retrospective cohort study

Author

Mallabar-Rimmer, Bethan, primary, Merriel, Samuel WD, additional, Webster, Amy P, additional, Wood, Andrew R, additional, Barclay, Matthew, additional, Tyrrell, Jessica, additional, Ruth, Katherine S, additional, Thirlwell, Christina, additional, Oram, Richard, additional, Weedon, Michael N, additional, Bailey, Sarah ER, additional, and Green, Harry D, additional

Published
2023
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11. Hyperglycaemia is a causal risk factor for upper limb pathologies.

Author

Green, Harry D, Burden, Ella, Chen, Ji, Evans, Jonathan, Patel, Kashyap, Wood, Andrew R, Beaumont, Robin N, Tyrrell, Jessica, Frayling, Timothy M, Hattersley, Andrew T, Oram, Richard A, Bowden, Jack, Barroso, Inês, Smith, Christopher, and Weedon, Michael N

Subjects
*CARPAL tunnel syndrome, *HYPERGLYCEMIA, *MUSCULOSKELETAL system diseases, *FAT, *DIABETES complications, *GENETIC techniques
Abstract

Background Diabetes (regardless of type) and obesity are associated with a range of musculoskeletal disorders. The causal mechanisms driving these associations are unknown for many upper limb pathologies. We used genetic techniques to test the causal link between glycemia, obesity and musculoskeletal conditions. Methods In the UK Biobank's unrelated European cohort (N  = 379 708) we performed mendelian randomisation (MR) analyses to test for a causal effect of long-term high glycaemia and adiposity on four musculoskeletal pathologies: frozen shoulder, Dupuytren's disease, carpal tunnel syndrome and trigger finger. We also performed single-gene MR using rare variants in the GCK gene. Results Using MR, we found evidence that long-term high glycaemia has a causal role in the aetiology of upper limb conditions. A 10-mmol/mol increase in genetically predicted haemoglobin A1C (HbA1c) was associated with frozen shoulder: odds ratio (OR) = 1.50 [95% confidence interval (CI), 1.20–1.88], Dupuytren's disease: OR = 1.17 (95% CI, 1.01–1.35), trigger finger: OR = 1.30 (95% CI, 1.09–1.55) and carpal tunnel syndrome: OR = 1.20 (95% CI, 1.09–1.33). Carriers of GCK mutations have increased odds of frozen shoulder: OR = 7.16 (95% CI, 2.93–17.51) and carpal tunnel syndrome: OR = 2.86 (95% CI, 1.50–5.44) but not Dupuytren's disease or trigger finger. We found evidence that an increase in genetically predicted body mass index (BMI) of 5 kg/m2 was associated with carpal tunnel syndrome: OR = 1.13 (95% CI, 1.10–1.16) and associated negatively with Dupuytren's disease: OR = 0.94 (95% CI, 0.90–0.98), but no evidence of association with frozen shoulder or trigger finger. Trigger finger (OR 1.96 (95% CI, 1.42–2.69) P  =   3.6e-05) and carpal tunnel syndrome [OR 1.63 (95% CI, 1.36–1.95) P  =   8.5e-08] are associated with genetically predicted unfavourable adiposity increase of one standard deviation of body fat. Conclusions Our study consistently demonstrates a causal role of long-term high glycaemia in the aetiology of upper limb musculoskeletal conditions. Clinicians treating diabetes patients should be aware of these complications in clinic, specifically those managing the care of GCK mutation carriers. Upper limb musculoskeletal conditions should be considered diabetes complications. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank

Author

Green, Harry D, primary, Merriel, Samuel WD, additional, Oram, Richard A, additional, Ruth, Katherine S, additional, Tyrrell, Jessica, additional, Jones, Samuel E, additional, Thirlwell, Chrissie, additional, Gillings, Mireille, additional, Weedon, Michael N, additional, and Bailey, Sarah ER, additional

Published
2022
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16. Genetically defined favourable adiposity is not associated with a clinically meaningful difference in clinical course in people with type 2 diabetes but does associate with a favourable metabolic profile

Author

Heald, Adrian H., primary, Martin, Susan, additional, Fachim, Helene, additional, Green, Harry D., additional, Young, Katherine G., additional, Malipatil, Nagaraj, additional, Siddals, Kirk, additional, Cortes, Gabriela, additional, Tyrrell, Jessica, additional, Wood, Andrew R, additional, Beaumont, Robin N., additional, Frayling, Timothy M., additional, Donn, Rachelle, additional, Narayanan, Ram Prakash, additional, Ollier, William, additional, Gibson, Martin, additional, and Yaghootkar, Hanieh, additional

Published
2021
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17. P118 Positivity thresholds of total infliximab and adalimumab anti-drug antibody assays and impact in clinical practice

Author

Nice, Rachel, primary, Chanchlani, Neil, additional, Kennedy, Nicholas A, additional, Green, Harry D, additional, Lin, Simeng, additional, Gordon, Claire, additional, Chee, Desmond, additional, Hamilton, Benjamin, additional, Bewshea, Claire, additional, Goodhand, James, additional, Ahmad, Tariq, additional, McDonald, Timothy, additional, and Perry, Mandy, additional

Published
2021
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19. Genetic evidence that higher central adiposity causes gastro-oesophageal reflux disease: a Mendelian randomization study

Author

Green, Harry D, primary, Beaumont, Robin N, additional, Wood, Andrew R, additional, Hamilton, Benjamin, additional, Jones, Samuel E, additional, Goodhand, James R, additional, Kennedy, Nicholas A, additional, Ahmad, Tariq, additional, Yaghootkar, Hanieh, additional, Weedon, Michael N, additional, Frayling, Timothy M, additional, and Tyrrell, Jessica, additional

Published
2020
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20. Quality improvement project identifies factors associated with delay in IBD diagnosis

Author

Walker, Gareth J., primary, Lin, Simeng, additional, Chanchlani, Neil, additional, Thomas, Amanda, additional, Hendy, Peter, additional, Heerasing, Neel, additional, Moore, Lucy, additional, Green, Harry D., additional, Chee, Desmond, additional, Bewshea, Claire, additional, Mays, Joseph, additional, Kennedy, Nicholas A., additional, Ahmad, Tariq, additional, and Goodhand, James R., additional

Published
2020
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21. Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment

Author

Lin, Simeng, primary, Green, Harry D, additional, Hendy, Peter, additional, Heerasing, Neel M, additional, Chanchlani, Neil, additional, Hamilton, Benjamin, additional, Walker, Gareth J, additional, Heap, Graham A, additional, Hobart, Jeremy, additional, Martin, Roswell J, additional, Coles, Alasdair J, additional, Silverberg, Mark S, additional, Irving, Peter M, additional, Chung-Faye, Guy, additional, Silber, Eli, additional, Cummings, J R Fraser, additional, Lytvyak, Ellina, additional, Andersen, Vibeke, additional, Wood, Andrew R, additional, Tyrrell, Jessica, additional, Beaumont, Robin N, additional, Weedon, Michael N, additional, Kennedy, Nicholas A, additional, Spiers, Alexander, additional, Harrower, Timothy, additional, Goodhand, James R, additional, and Ahmad, Tariq, additional

Published
2020
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22. Genome-Wide Association Study of Microscopic Colitis in the UK Biobank Confirms Immune-Related Pathogenesis

Author

Green, Harry D, primary, Beaumont, Robin N, additional, Thomas, Amanda, additional, Hamilton, Benjamin, additional, Wood, Andrew R, additional, Sharp, Seth, additional, Jones, Samuel E, additional, Tyrrell, Jessica, additional, Walker, Gareth, additional, Goodhand, James, additional, Kennedy, Nicholas A, additional, Ahmad, Tariq, additional, and Weedon, Michael N, additional

Published
2019
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23. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study

Author

Kennedy, Nicholas A, primary, Heap, Graham A, additional, Green, Harry D, additional, Hamilton, Benjamin, additional, Bewshea, Claire, additional, Walker, Gareth J, additional, Thomas, Amanda, additional, Nice, Rachel, additional, Perry, Mandy H, additional, Bouri, Sonia, additional, Chanchlani, Neil, additional, Heerasing, Neel M, additional, Hendy, Peter, additional, Lin, Simeng, additional, Gaya, Daniel R, additional, Cummings, J R Fraser, additional, Selinger, Christian P, additional, Lees, Charlie W, additional, Hart, Ailsa L, additional, Parkes, Miles, additional, Sebastian, Shaji, additional, Mansfield, John C, additional, Irving, Peter M, additional, Lindsay, James, additional, Russell, Richard K, additional, McDonald, Timothy J, additional, McGovern, Dermot, additional, Goodhand, James R, additional, Ahmad, Tariq, additional, Patel, Vinod, additional, Mazhar, Zia, additional, Saich, Rebecca, additional, Colleypriest, Ben, additional, Tham, Tony C, additional, Iqbal, Tariq H, additional, Kaushik, Vishal, additional, Murugesan, Senthil, additional, Singh, Salil, additional, Weaver, Sean, additional, Preston, Cathryn, additional, Butt, Assad, additional, Smith, Melissa, additional, Basude, Dharamveer, additional, Beale, Amanda, additional, Langlands, Sarah, additional, Direkze, Natalie, additional, Torrente, Franco, additional, De La Revella Negro, Juan, additional, MacDonald, Chris Ewen, additional, Evans, Stephen M, additional, Gunasekera, Anton V J, additional, Thakur, Alka, additional, Elphick, David, additional, Shenoy, Achuth, additional, Nwokolo, Chuka U, additional, Dhar, Anjan, additional, Cole, Andrew T, additional, Agrawal, Anurag, additional, Bridger, Stephen, additional, Doherty, Julie, additional, Cooper, Sheldon C, additional, de Silva, Shanika, additional, Mowat, Craig, additional, Mayhead, Phillip, additional, Lees, Charlie, additional, Jones, Gareth, additional, Hart, James W, additional, Gervais, Lisa, additional, Dunckley, Paul, additional, Mahmood, Tariq, additional, Banim, Paul J R, additional, Sonwalkar, Sunil, additional, Ghosh, Deb, additional, Phillips, Rosemary H, additional, Azaz, Amer, additional, Shenderey, Richard, additional, Armstrong, Lawrence, additional, Bell, Claire, additional, Hariraj, Radhakrishnan, additional, Matthews, Helen, additional, Jafferbhoy, Hasnain, additional, Zamvar, Veena, additional, De Caestecker, John S, additional, Willmott, Anne, additional, Miller, Richard, additional, Babu, Palani Sathish, additional, Tzivinikos, Christos, additional, Bloom, Stuart L, additional, Chung-Faye, Guy, additional, Croft, Nicholas M, additional, Fell, John ME, additional, Harbord, Marcus, additional, Hart, Ailsa, additional, Hope, Ben, additional, Lindsay, James O, additional, Mawdsley, Joel E, additional, McNair, Alistair, additional, Monahan, Kevin J, additional, Murray, Charles D, additional, Orchard, Timothy, additional, Paul, Thankam, additional, Pollok, Richard, additional, Shah, Neil, additional, Johnson, Matt W, additional, Modi, Anita, additional, Kabiru, Kasamu Dawa, additional, Baburajan, B K, additional, Bhaduri, Bim, additional, Fagbemi, Andrew Adebayo, additional, Levison, Scott, additional, Limdi, Jimmy K, additional, Watts, Gill, additional, Foley, Stephen, additional, Ramadas, Arvind, additional, MacFaul, George, additional, Mansfield, John, additional, Grellier, Leonie, additional, Morris, Mary-Anne, additional, Tremelling, Mark, additional, Hawkey, Chris, additional, Kirkham, Sian, additional, Charlton, Charles PJ, additional, Rodrigues, Astor, additional, Simmons, Alison, additional, Lewis, Stephen J, additional, Snook, Jonathon, additional, Tighe, Mark, additional, Goggin, Patrick M, additional, De Silva, Aminda N, additional, Lal, Simon, additional, Smith, Mark S, additional, Panter, Simon, additional, Dharmisari, Suranga, additional, Carter, Martyn, additional, Watts, David, additional, Mahmood, Zahid, additional, McLain, Bruce, additional, Sen, Sandip, additional, Pigott, Anna J, additional, Hobday, David, additional, Wesley, Emma, additional, Johnston, Richard, additional, Edwards, Cathryn, additional, Beckly, John, additional, Vani, Deven, additional, Ramakrishnan, Subramaniam, additional, Chaudhary, Rakesh, additional, Trudgill, Nigel J, additional, Cooney, Rachel, additional, Bell, Andy, additional, Prasad, Neeraj, additional, Gordon, John N, additional, Brookes, Matthew J, additional, Li, Andy, additional, and Gore, Stephen, additional

Published
2019
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24. Signal Reconstruction of Pulmonary Vein Recordings Using a Phenomenological Mathematical Model: Application to Pulmonary Vein Isolation Therapy

Author

Green, Harry D., Thomas, Glyn, and Terry, John R.

Subjects
pulmonary vein recording, Physiology, cardiology, minimal cardiac models, cardiovascular system, atrial fibrillation, signal reconstruction, radiofrequency ablation, pulmonary vein isolation, mathematical model
Abstract

Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is commonly initiated by ectopic beats originating from a small myocardial sleeve extending over the pulmonary veins. Pulmonary vein isolation therapy attempts to isolate the pulmonary veins from the left atrium by ablating tissue, commonly by using radiofrequency ablation. During this procedure, the cardiologist records electrical activity using a lasso catheter, and the activation pattern recorded is used as a guide toward which regions to ablate. However, poor contact between electrode and tissue can lead to important regions of electrical activity not being recorded in clinic. We reproduce these signals through the use of a phenomenological model of the cardiac action potential on a cylinder, which we fit to post-AF atrial cells, and model the bipolar electrodes of the lasso catheter by an approximation of the surface potential. The resulting activation pattern is validated by direct comparison with those of clinical recordings. A potential application of the model is to reconstruct the missing electrical activity, minimizing the impact of the information loss on the clinical procedure, and we present results to demonstrate this.

Published
2017
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25. Understanding Anti-TNF Treatment Failure: A Prospective Multi-Centre Study of Biologic Naïve Patients with Active Luminal Crohn's Disease

Author

Kennedy, Nicholas A, primary, Heap, Graham A, additional, Green, Harry D, additional, Hamilton, Benjamin, additional, Bewshea, Claire, additional, Walker, Gareth J, additional, Thomas, Amanda, additional, Nice, Rachel, additional, Perry, Mandy H, additional, Bouri, Sonia, additional, Chanchlani, Neil, additional, Heerasing, Neel M, additional, Hendy, Peter, additional, Lin, Simeng, additional, Gaya, Daniel R, additional, Cummings, JR Fraser, additional, Lees, Charlie W, additional, Hart, Ailsa L, additional, Parkes, Miles, additional, Sebastian, Shaji, additional, Mansfield, John C, additional, Irving, Peter M, additional, Lindsay, James, additional, Russell, Richard K, additional, McDonald, Timothy, additional, McGovern, Dermot, additional, Group, IBD Pharmacogenetics Study, additional, Goodhand, James R, additional, and Ahmad, Tariq, additional

Published
2018
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27. Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment

Author

Peter M. Irving, Guy Chung-Faye, Nicholas A. Kennedy, Tariq Ahmad, Ellina Lytvyak, Alexander Spiers, James R Goodhand, Timothy Harrower, Neil Chanchlani, Gareth J. Walker, Graham A. Heap, Harry D Green, JR Fraser Cummings, Alasdair Coles, Neel Heerasing, Eli Silber, Andrew R. Wood, R. Martin, Peter Hendy, Michael N. Weedon, Benjamin Hamilton, Mark S. Silverberg, Jeremy Hobart, Robin N Beaumont, Jessica Tyrrell, Simeng Lin, Vibeke Andersen, Lin, Simeng [0000-0002-4201-4879], Green, Harry D [0000-0002-5105-184X], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Multiple Sclerosis, Gastroenterology, State Medicine, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Genetic predisposition, Humans, Prospective Studies, Genetic risk, Prospective cohort study, Retrospective Studies, business.industry, Multiple sclerosis, Significant difference, anti-TNF, General Medicine, Middle Aged, medicine.disease, Spinal cord, 030104 developmental biology, medicine.anatomical_structure, Case-Control Studies, Concomitant, Female, Tumor Necrosis Factor Inhibitors, Tumor necrosis factor alpha, Demyelination, business, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract

Background Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. Methods We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. Results Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7–63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1–28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10–4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10–3, SD 0.0042] [p = 0.23]. Conclusions Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.

Published
2020
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