17 results on '"Green, Harry D"'
Search Results
2. Response to Penetrance estimates of hereditary cancers in a population setting using UK Biobank data
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Jackson, Leigh, Weedon, Michael N., Green, Harry D., Mallabar-Rimmer, Bethan, Harrison, Jamie W., Wood, Andrew R., Ruth, Katherine S., Tyrrell, Jess, and Wright, Caroline F.
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- 2024
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3. Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis
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Loginovic, Pavel, Wang, Feiyi, Li, Jiang, Ferrat, Lauric, Mirshahi, Uyenlinh L., Rao, H. Shanker, Petzold, Axel, Tyrrell, Jessica, Green, Harry D., Weedon, Michael N., Ganna, Andrea, Tuomi, Tiinamaija, Carey, David J., Oram, Richard A., and Braithwaite, Tasanee
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- 2024
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4. The effect of pregnancy vitamin D supplementation on offspring bone mineral density in childhood: a systematic review and meta-analysis
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Moon, Rebecca J., Green, Harry D., D’Angelo, Stefania, Godfrey, Keith M., Davies, Justin H., Curtis, Elizabeth M., Cooper, Cyrus, and Harvey, Nicholas C.
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- 2023
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5. Influence of family history on penetrance of hereditary cancers in a population setting
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Jackson, Leigh, Weedon, Michael N., Green, Harry D., Mallabar-Rimmer, Bethan, Harrison, Jamie W., Wood, Andy R., Ruth, Kate S., Tyrrell, Jess, and Wright, Caroline F.
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- 2023
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6. 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
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Green, Harry D., Merriel, Samuel W. D., Oram, Richard A., Ruth, Katherine S., Tyrrell, Jessica, Jones, Samuel E., Thirlwell, Chrissie, Weedon, Michael N., and Bailey, Sarah E. R.
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- 2022
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7. Response to: Genetic risk scores may compound rather than solve the issue of prostate cancer overdiagnosis (BJC-LT3342090)
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Green, Harry D., Merriel, Samuel W. D., Oram, Richard A., Ruth, Katherine S., Tyrrell, Jessica, Jones, Samuel E., Thirlwell, Chrissie, Weedon, Michael N., and Bailey, Sarah E. R.
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- 2023
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8. Type 1 Diabetes Genetic Risk Contributes to Phenotypic Presentation in Monogenic Autoimmune Diabetes.
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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
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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
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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
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- 2019
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10. Hyperglycaemia is a causal risk factor for upper limb pathologies.
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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
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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]
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- 2024
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11. 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.
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Heald, Adrian H., Martin, Susan, Fachim, Helene, Green, Harry D., Young, Katherine G., Malipatil, Nagaraj, Siddals, Kirk, Cortes, Gabriela, Tyrrell, Jessica, Wood, Andrew R, Beaumont, Robin N., Frayling, Timothy M., Donn, Rachelle, Narayanan, Ram Prakash, Ollier, William, Gibson, Martin, and Yaghootkar, Hanieh
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DISEASE progression ,TRIGLYCERIDES ,ANTIHYPERTENSIVE agents ,BODY weight ,STROKE ,ANTILIPEMIC agents ,CROSS-sectional method ,EFFECT sizes (Statistics) ,MYOCARDIAL infarction ,TYPE 2 diabetes ,DISEASE susceptibility ,DESCRIPTIVE statistics ,BODY mass index ,HIGH density lipoproteins ,ODDS ratio ,ADIPOSE tissues ,LONGITUDINAL method - Abstract
Aims: Change in weight, HbA1c, lipids, blood pressure and cardiometabolic events over time is variable in individuals with type 2 diabetes. We hypothesised that people with a genetic predisposition to a more favourable adiposity distribution could have a less severe clinical course/progression. Methods: We involved people with type 2 diabetes from two UK‐based cohorts: 11,914 individuals with GP follow‐up data from the UK Biobank and 723 from Salford. We generated a 'favourable adiposity' genetic score and conducted cross‐sectional and longitudinal studies to test its association with weight, BMI, lipids, blood pressure, medication use and risk of myocardial infarction and stroke using 15 follow‐up time points with 1‐year intervals. Results: The 'favourable adiposity' genetic score was cross‐sectionally associated with higher weight (effect size per 1 standard deviation higher genetic score: 0.91 kg [0.59,1.23]) and BMI (0.30 kg/m2 [0.19,0.40]), but higher high‐density lipoprotein (0.02 mmol/L [0.01,0.02]) and lower triglycerides (−0.04 mmol/L [−0.07, −0.02]) in the UK Biobank at baseline, and this pattern of association was consistent across follow‐up. There was a trend for participants with higher 'favourable adiposity' genetic score to have lower risk of myocardial infarction and/or stroke (odds ratio 0.79 [0.62, 1.00]) compared to those with lower score. A one standard deviation higher score was associated with lower odds of using lipid‐lowering (0.91 [0.86, 0.97]) and anti‐hypertensive medication (0.95 [0.91, 0.99]). Conclusions: In individuals with type 2 diabetes, having more 'favourable adiposity' alleles is associated with a marginally better lipid profile long‐term and having lower odds of requiring lipid‐lowering or anti‐hypertensive medication in spite of relatively higher adiposity. [ABSTRACT FROM AUTHOR]
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- 2021
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12. A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.
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Green, Harry D., Jones, Alistair, Evans, Jonathan P., Wood, Andrew R., Beaumont, Robin N., Tyrrell, Jessica, Frayling, Timothy M., Smith, Christopher, and Weedon, Michael N.
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GENOME-wide association studies , *DIABETES , *TYPE 1 diabetes , *ARTIFICIAL pancreases , *SHOULDER , *INSULIN pumps , *ETIOLOGY of diabetes - Abstract
Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40–60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16–1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren's disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02–1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren's disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition. Author summary: Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40–60 years. Little is known about the causes but it is known to be more common in people with diabetes. In a dataset of 500,000 people, we used a genome-wide association study to find genetic causes and a genetic technique called Mendelian randomisation to test if diabetes causes frozen shoulder. We found five new genetic variants that associate with frozen shoulder, and showed genetic overlap with Dupuytren's Disease, a similar condition that affects the fingers. We found an association with diabetes and obesity, but that the obesity association disappeared when we accounted for diabetes status, suggesting the condition is glycaemic rather than mechanical. Our Mendelian randomisation study showed evidence that type 1 diabetes has a causal effect on development of frozen shoulder, likely through a pathway involving long-term high blood glucose levels. [ABSTRACT FROM AUTHOR]
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- 2021
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13. Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.
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Lin, Simeng, Green, Harry D, Hendy, Peter, Heerasing, Neel M, Chanchlani, Neil, Hamilton, Benjamin, Walker, Gareth J, Heap, Graham A, Hobart, Jeremy, Martin, Roswell J, Coles, Alasdair J, Silverberg, Mark S, Irving, Peter M, Chung-Faye, Guy, Silber, Eli, Cummings, J R Fraser, Lytvyak, Ellina, Andersen, Vibeke, Wood, Andrew R, and Tyrrell, Jessica
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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. [ABSTRACT FROM AUTHOR]- Published
- 2020
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14. Genetic evidence that higher central adiposity causes gastro-oesophageal reflux disease: a Mendelian randomization study.
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Green, Harry D, Beaumont, Robin N, Wood, Andrew R, Hamilton, Benjamin, Jones, Samuel E, Goodhand, James R, Kennedy, Nicholas A, Ahmad, Tariq, Yaghootkar, Hanieh, Weedon, Michael N, Frayling, Timothy M, and Tyrrell, Jessica
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OBESITY , *WAIST-hip ratio , *SMOKING , *CARDIOVASCULAR diseases risk factors , *BIRTH size , *BODY mass index , *COFFEE drinks , *WAIST circumference - Abstract
Background: Gastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MR)] to identify potential causal modifiable risk factors for GORD.Methods: We used data from 451 097 European participants in the UK Biobank and defined GORD using hospital-defined ICD10 and OPCS4 codes and self-report data (N = 41 024 GORD cases). We tested observational and MR-based associations between GORD and four adiposity measures [body mass index (BMI), waist-hip ratio (WHR), a metabolically favourable higher body-fat percentage and waist circumference], smoking status, smoking frequency and caffeine consumption.Results: Observationally, all adiposity measures were associated with higher odds of GORD. Ever and current smoking were associated with higher odds of GORD. Coffee consumption was associated with lower odds of GORD but, among coffee drinkers, more caffeinated-coffee consumption was associated with higher odds of GORD. Using MR, we provide strong evidence that higher WHR and higher WHR adjusted for BMI lead to GORD. There was weak evidence that higher BMI, body-fat percentage, coffee drinking or smoking caused GORD, but only the observational effects for BMI and body-fat percentage could be excluded. This MR estimated effect for WHR equates to a 1.23-fold higher odds of GORD per 5-cm increase in waist circumference.Conclusions: These results provide strong evidence that a higher waist-hip ratio leads to GORD. Our study suggests that central fat distribution is crucial in causing GORD rather than overall weight. [ABSTRACT FROM AUTHOR]- Published
- 2020
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15. Quality improvement project identifies factors associated with delay in IBD diagnosis.
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Walker, Gareth J., Lin, Simeng, Chanchlani, Neil, Thomas, Amanda, Hendy, Peter, Heerasing, Neel, Moore, Lucy, Green, Harry D., Chee, Desmond, Bewshea, Claire, Mays, Joseph, Kennedy, Nicholas A., Ahmad, Tariq, and Goodhand, James R.
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INFLAMMATORY bowel diseases ,CROHN'S disease ,SECONDARY care (Medicine) ,ULCERATIVE colitis ,DISEASE progression - Abstract
Summary: Background: Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking. Aim: To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD. Methods: This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Outcome measures were demographic, clinical and laboratory factors associated with a delayed time, defined as greater than upper quartile, to: (a) patient presentation (b) GP referral (c) secondary care diagnosis, and factors associated with a complicated disease course (hospitalisation and/or surgery and/or biologic treatment) in the year after diagnosis. Results: The median [IQR] diagnosis sub‐intervals were: (a) patient = 2.1 months [0.9‐5.1]; (b) GP = 0.3 months [0.0‐0.9]; (c) secondary care = 1.1 months [0.5‐2.1]. 50% of patients were diagnosed within 4 months and 92% were diagnosed within 2 years of symptom onset. Diagnostic delay was more common in Crohn's disease (7.6 months [3.1‐15.0]) than ulcerative colitis (3.3 months [1.9‐7.3]) (P < 0.001). Patients who presented as an emergency (P < 0.001) but not those with a delayed overall time to diagnosis (P = 0.35) were more likely to have a complicated disease course. Conclusion: Time to patient presentation is the largest component of time to IBD diagnosis. Emergency presentation is common and, unlike a delayed time to diagnosis, is associated with a complicated disease course. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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16. Genome-Wide Association Study of Microscopic Colitis in the UK Biobank Confirms Immune-Related Pathogenesis.
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Green, Harry D, Beaumont, Robin N, Thomas, Amanda, Hamilton, Benjamin, Wood, Andrew R, Sharp, Seth, Jones, Samuel E, Tyrrell, Jessica, Walker, Gareth, Goodhand, James, Kennedy, Nicholas A, Ahmad, Tariq, and Weedon, Michael N
- Abstract
Background and Aims The causes of microscopic colitis are currently poorly understood. Previous reports have found clinical associations with coeliac disease and genetic associations at the human leukocyte antigen [HLA] locus on the ancestral 8.1 haplotype. We investigated pharmacological and genetic factors associated with microscopic colitis in the UK Biobank. Methods In total, 483 European UK Biobank participants were identified by ICD10 coding, and a genome-wide association study was performed using BOLT-LMM, with a sensitivity analysis performed excluding potential confounders. The HLA*IMP:02 algorithm was used to estimate allele frequency at 11 classical HLA genes, and downstream analysis was performed using FUMA. Genetic overlap with inflammatory bowel disease [Crohn's disease and ulcerative colitis] was investigated using genetic risk scores. Results We found significant phenotypic associations with smoking status, coeliac disease and the use of proton-pump inhibitors but not with other commonly reported pharmacological risk factors. Using the largest sample size to date, we confirmed a recently reported association with the MHC Ancestral 8.1 Haplotype. Downstream analysis suggests association with digestive tract morphogenesis. By calculating genetic risk scores, we also report suggestive evidence of shared genetic risk with Crohn's disease, but not with ulcerative colitis. Conclusions This report confirms the role of genetic determinants in the HLA in the pathogenesis of microscopic colitis. The genetic overlap with Crohn's disease suggests a common underlying mechanism of disease. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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17. Signal Reconstruction of Pulmonary Vein Recordings Using a Phenomenological Mathematical Model: Application to Pulmonary Vein Isolation Therapy.
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Green, Harry D., Thomas, Glyn, and Terry, John R.
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MATHEMATICAL models ,PULMONARY veins ,ISOLATION (Hospital care) ,ATRIAL fibrillation ,ARRHYTHMIA prevention - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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- View/download PDF
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