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15 results on '"Brooks, Claire"'

1. Synchronization in Retrospective Respiratory Gating using Deep Learning

Author

Bayo, Fernando, Brooks, Claire J., Pérez Benito, David, López Expósito, Patricio, Vaquero, Juan José, Bayo, Fernando, Brooks, Claire J., Pérez Benito, David, López Expósito, Patricio, and Vaquero, Juan José

Abstract

Breathing motion introduces artifacts during CT acquisition, what affect the quality and subsequent reconstruction of the images. This study aims to reduce artefact in CT images using deep learning techniques. Specifically, we propose the implementation of an autoencoder based on convolutional neural networks. Once the model was trained, we employed a morphing technique to generate new images with reduced respiratory motion. By analyzing the respiratory signal, we classified the different images into phases and selected those most suitable for correction. Subsequently, we applied the de- scribed method, obtaining a more homogeneous data set. The results demonstrate a significant reduction in motion when comparing intensity changes within the regions most affected by motion. Thus, we validated the efficacy of the proposed approach to mitigate breathing-induced artifacts. The appli- cation of artificial intelligence (AI) in this field represents a significant advance. This study provides promising initial results and opens up new possibilities for research and de- velopment. By complementing existing techniques, AI offers enhanced motion reduction capabilities, thus improving the quality of CT images. The potential for future advances in this direction are substantial, promising further reduction in respiratory motion artifacts and improvement to the overall quality of CT images.

Published
2023

2. Isometric force pillow: using air pressure to quantify involuntary finger flexion in the presence of hypertonia

Author

Seim, Caitlyn E., Han, Chuzhang, Lowber, Alexis J., Brooks, Claire, Payne, Marie, Lansberg, Maarten G., Flavin, Kara E., Dewald, Julius P. A., Okamura, Allison M., Seim, Caitlyn E., Han, Chuzhang, Lowber, Alexis J., Brooks, Claire, Payne, Marie, Lansberg, Maarten G., Flavin, Kara E., Dewald, Julius P. A., and Okamura, Allison M.

Abstract

Survivors of central nervous system injury commonly present with spastic hypertonia. The affected muscles are hyperexcitable and can display involuntary static muscle tone and an exaggerated stretch reflex. These symptoms affect posture and disrupt activities of daily living. Symptoms are typically measured using subjective manual tests such as the Modified Ashworth Scale; however, more quantitative measures are necessary to evaluate potential treatments. The hands are one of the most common targets for intervention, but few investigators attempt to quantify symptoms of spastic hypertonia affecting the fingers. We present the isometric force pillow (IFP) to quantify involuntary grip force. This lightweight, computerized tool provides a holistic measure of finger flexion force and can be used in various orientations for clinical testing and to measure the impact of assistive devices.

Published
2020
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3. Chemoprevention of esophageal cancer with esomeprazole and aspirin therapy: Efficacy and safety in the phase III randomized factorial ASPECT trial

Author

Jankowski, Janusz, de Caestecker, John, Love, Sharon, Reilly, Gavin, Ang, Yeng, Ragunath, Krish, Tucker, Arthur, Penman, Ian, Rodgers, Colin, Roffe, Emma, Brooks, Claire E., Attwood, Stephen, Morris, Danielle, Harrison, Rebecca, Bhandari, Pradeep, Watson, Peter, Sanders, Scott, Barr, Hugh, Moayyedi, Paul, Neale, James, Jankowski, Janusz, de Caestecker, John, Love, Sharon, Reilly, Gavin, Ang, Yeng, Ragunath, Krish, Tucker, Arthur, Penman, Ian, Rodgers, Colin, Roffe, Emma, Brooks, Claire E., Attwood, Stephen, Morris, Danielle, Harrison, Rebecca, Bhandari, Pradeep, Watson, Peter, Sanders, Scott, Barr, Hugh, Moayyedi, Paul, and Neale, James

Abstract

LBA4008 Background: Esophageal adenocarcinoma (EA) is the sixth most common cause of global cancer death. We rely on endoscopy screening to identify and monitor patients with Barrett’s esophagus (BE) and find neoplastic lesions early enough to manage their EA. This approach has a modest effect on EA supported by low quality evidence. We evaluated the efficacy of aspirin and high dose acid suppression in preventing EA in patients with BE. Methods: We recruited patients with ≥ 1cm of BE and no high grade dysplasia (HGD) or EA at baseline in UK and Canadian hospitals. To conceal allocation, a central trials unit randomized patients using a computer-generated schedule. Patients were randomized unblinded 1:1:1:1 in a 2X2 factorial design to high dose (40mg twice daily) or low dose (20mg once daily) esomeprazole proton pump inhibitor acid suppression (PPI), alone or combined with low dose aspirin 300mg/day (330mg in Canada). The primary composite endpoint was time to all-cause mortality or EA or HGD analyzed using accelerated failure time modelling adjusting for minimization factors (age, length of Barrett’s esophagus and presence of intestinal metaplasia). Results: We recruited 2563 Barrett’s patients followed-up for a median of 8.9 years (interquartile range 8.2-9.8) with 20,095 years of follow up. There were 313 events of the composite primary endpoint. High dose PPI was statistically significantly superior to low dose PPI (p = 0.037, N = 2535, time ratio (TR) 1.27, 95% CI = 1.01-1.58). Aspirin therapy showed a trend to benefit but was not statistically significant (p = 0.068, N = 2280, TR = 1.24, 95% CI = 0.98 – 1.57). The combination of aspirin with high dose PPI had the strongest effect compared to low dose PPI with no aspirin (TR = 1.59, 95% CI = 1.14 to 2.23, p = 0.007). There were few serious adverse events reported (1.0% of patients), with 99.9% data collected. Conclusions: This is the largest randomized controlled chemoprevention trial in patients with Barrett’

Published
2018

4. Chemoprevention of esophageal cancer with esomeprazole and aspirin therapy: Efficacy and safety in the phase III randomized factorial ASPECT trial

Author

Jankowski, Janusz, de Caestecker, John, Love, Sharon, Reilly, Gavin, Ang, Yeng, Ragunath, Krish, Tucker, Arthur, Penman, Ian, Rodgers, Colin, Roffe, Emma, Brooks, Claire E., Attwood, Stephen, Morris, Danielle, Harrison, Rebecca, Bhandari, Pradeep, Watson, Peter, Sanders, Scott, Barr, Hugh, Moayyedi, Paul, Neale, James, Jankowski, Janusz, de Caestecker, John, Love, Sharon, Reilly, Gavin, Ang, Yeng, Ragunath, Krish, Tucker, Arthur, Penman, Ian, Rodgers, Colin, Roffe, Emma, Brooks, Claire E., Attwood, Stephen, Morris, Danielle, Harrison, Rebecca, Bhandari, Pradeep, Watson, Peter, Sanders, Scott, Barr, Hugh, Moayyedi, Paul, and Neale, James

Abstract

LBA4008 Background: Esophageal adenocarcinoma (EA) is the sixth most common cause of global cancer death. We rely on endoscopy screening to identify and monitor patients with Barrett’s esophagus (BE) and find neoplastic lesions early enough to manage their EA. This approach has a modest effect on EA supported by low quality evidence. We evaluated the efficacy of aspirin and high dose acid suppression in preventing EA in patients with BE. Methods: We recruited patients with ≥ 1cm of BE and no high grade dysplasia (HGD) or EA at baseline in UK and Canadian hospitals. To conceal allocation, a central trials unit randomized patients using a computer-generated schedule. Patients were randomized unblinded 1:1:1:1 in a 2X2 factorial design to high dose (40mg twice daily) or low dose (20mg once daily) esomeprazole proton pump inhibitor acid suppression (PPI), alone or combined with low dose aspirin 300mg/day (330mg in Canada). The primary composite endpoint was time to all-cause mortality or EA or HGD analyzed using accelerated failure time modelling adjusting for minimization factors (age, length of Barrett’s esophagus and presence of intestinal metaplasia). Results: We recruited 2563 Barrett’s patients followed-up for a median of 8.9 years (interquartile range 8.2-9.8) with 20,095 years of follow up. There were 313 events of the composite primary endpoint. High dose PPI was statistically significantly superior to low dose PPI (p = 0.037, N = 2535, time ratio (TR) 1.27, 95% CI = 1.01-1.58). Aspirin therapy showed a trend to benefit but was not statistically significant (p = 0.068, N = 2280, TR = 1.24, 95% CI = 0.98 – 1.57). The combination of aspirin with high dose PPI had the strongest effect compared to low dose PPI with no aspirin (TR = 1.59, 95% CI = 1.14 to 2.23, p = 0.007). There were few serious adverse events reported (1.0% of patients), with 99.9% data collected. Conclusions: This is the largest randomized controlled chemoprevention trial in patients with Barrett’

Published
2018

5. Sarin Exposures in A Cohort of British Military Participants in Human Experimental Research at Porton Down 1945-1987

Author

Keegan, Thomas J., Carpenter, Lucy M., Brooks, Claire, Langdon, Toby, Venables, Katherine M., Keegan, Thomas J., Carpenter, Lucy M., Brooks, Claire, Langdon, Toby, and Venables, Katherine M.

Abstract

Background The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK’s centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Objectives Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. Methods In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Results Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28–51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. Conclusions These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.

Published
2018

6. Sarin Exposures in A Cohort of British Military Participants in Human Experimental Research at Porton Down 1945-1987

Author

Keegan, Thomas J., Carpenter, Lucy M., Brooks, Claire, Langdon, Toby, Venables, Katherine M., Keegan, Thomas J., Carpenter, Lucy M., Brooks, Claire, Langdon, Toby, and Venables, Katherine M.

Abstract

Background The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK’s centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Objectives Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. Methods In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Results Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28–51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. Conclusions These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.

Published
2018

7. Chemoprevention of esophageal cancer with esomeprazole and aspirin therapy: Efficacy and safety in the phase III randomized factorial ASPECT trial

Author

Jankowski, Janusz, de Caestecker, John, Love, Sharon, Reilly, Gavin, Ang, Yeng, Ragunath, Krish, Tucker, Arthur, Penman, Ian, Rodgers, Colin, Roffe, Emma, Brooks, Claire E., Attwood, Stephen, Morris, Danielle, Harrison, Rebecca, Bhandari, Pradeep, Watson, Peter, Sanders, Scott, Barr, Hugh, Moayyedi, Paul, Neale, James, Jankowski, Janusz, de Caestecker, John, Love, Sharon, Reilly, Gavin, Ang, Yeng, Ragunath, Krish, Tucker, Arthur, Penman, Ian, Rodgers, Colin, Roffe, Emma, Brooks, Claire E., Attwood, Stephen, Morris, Danielle, Harrison, Rebecca, Bhandari, Pradeep, Watson, Peter, Sanders, Scott, Barr, Hugh, Moayyedi, Paul, and Neale, James

Abstract

LBA4008 Background: Esophageal adenocarcinoma (EA) is the sixth most common cause of global cancer death. We rely on endoscopy screening to identify and monitor patients with Barrett’s esophagus (BE) and find neoplastic lesions early enough to manage their EA. This approach has a modest effect on EA supported by low quality evidence. We evaluated the efficacy of aspirin and high dose acid suppression in preventing EA in patients with BE. Methods: We recruited patients with ≥ 1cm of BE and no high grade dysplasia (HGD) or EA at baseline in UK and Canadian hospitals. To conceal allocation, a central trials unit randomized patients using a computer-generated schedule. Patients were randomized unblinded 1:1:1:1 in a 2X2 factorial design to high dose (40mg twice daily) or low dose (20mg once daily) esomeprazole proton pump inhibitor acid suppression (PPI), alone or combined with low dose aspirin 300mg/day (330mg in Canada). The primary composite endpoint was time to all-cause mortality or EA or HGD analyzed using accelerated failure time modelling adjusting for minimization factors (age, length of Barrett’s esophagus and presence of intestinal metaplasia). Results: We recruited 2563 Barrett’s patients followed-up for a median of 8.9 years (interquartile range 8.2-9.8) with 20,095 years of follow up. There were 313 events of the composite primary endpoint. High dose PPI was statistically significantly superior to low dose PPI (p = 0.037, N = 2535, time ratio (TR) 1.27, 95% CI = 1.01-1.58). Aspirin therapy showed a trend to benefit but was not statistically significant (p = 0.068, N = 2280, TR = 1.24, 95% CI = 0.98 – 1.57). The combination of aspirin with high dose PPI had the strongest effect compared to low dose PPI with no aspirin (TR = 1.59, 95% CI = 1.14 to 2.23, p = 0.007). There were few serious adverse events reported (1.0% of patients), with 99.9% data collected. Conclusions: This is the largest randomized controlled chemoprevention trial in patients with Barrett’

Published
2018

8. Chemoprevention of esophageal cancer with esomeprazole and aspirin therapy: Efficacy and safety in the phase III randomized factorial ASPECT trial

Author

Jankowski, Janusz, de Caestecker, John, Love, Sharon, Reilly, Gavin, Ang, Yeng, Ragunath, Krish, Tucker, Arthur, Penman, Ian, Rodgers, Colin, Roffe, Emma, Brooks, Claire E., Attwood, Stephen, Morris, Danielle, Harrison, Rebecca, Bhandari, Pradeep, Watson, Peter, Sanders, Scott, Barr, Hugh, Moayyedi, Paul, Neale, James, Jankowski, Janusz, de Caestecker, John, Love, Sharon, Reilly, Gavin, Ang, Yeng, Ragunath, Krish, Tucker, Arthur, Penman, Ian, Rodgers, Colin, Roffe, Emma, Brooks, Claire E., Attwood, Stephen, Morris, Danielle, Harrison, Rebecca, Bhandari, Pradeep, Watson, Peter, Sanders, Scott, Barr, Hugh, Moayyedi, Paul, and Neale, James

Abstract

LBA4008 Background: Esophageal adenocarcinoma (EA) is the sixth most common cause of global cancer death. We rely on endoscopy screening to identify and monitor patients with Barrett’s esophagus (BE) and find neoplastic lesions early enough to manage their EA. This approach has a modest effect on EA supported by low quality evidence. We evaluated the efficacy of aspirin and high dose acid suppression in preventing EA in patients with BE. Methods: We recruited patients with ≥ 1cm of BE and no high grade dysplasia (HGD) or EA at baseline in UK and Canadian hospitals. To conceal allocation, a central trials unit randomized patients using a computer-generated schedule. Patients were randomized unblinded 1:1:1:1 in a 2X2 factorial design to high dose (40mg twice daily) or low dose (20mg once daily) esomeprazole proton pump inhibitor acid suppression (PPI), alone or combined with low dose aspirin 300mg/day (330mg in Canada). The primary composite endpoint was time to all-cause mortality or EA or HGD analyzed using accelerated failure time modelling adjusting for minimization factors (age, length of Barrett’s esophagus and presence of intestinal metaplasia). Results: We recruited 2563 Barrett’s patients followed-up for a median of 8.9 years (interquartile range 8.2-9.8) with 20,095 years of follow up. There were 313 events of the composite primary endpoint. High dose PPI was statistically significantly superior to low dose PPI (p = 0.037, N = 2535, time ratio (TR) 1.27, 95% CI = 1.01-1.58). Aspirin therapy showed a trend to benefit but was not statistically significant (p = 0.068, N = 2280, TR = 1.24, 95% CI = 0.98 – 1.57). The combination of aspirin with high dose PPI had the strongest effect compared to low dose PPI with no aspirin (TR = 1.59, 95% CI = 1.14 to 2.23, p = 0.007). There were few serious adverse events reported (1.0% of patients), with 99.9% data collected. Conclusions: This is the largest randomized controlled chemoprevention trial in patients with Barrett’

Published
2018

10. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.

Author

Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, Jankowski, Janusz A Z, Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, and Jankowski, Janusz A Z

Abstract

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Published
2012
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11. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Author

Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, Jankowski, Janusz, Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, and Jankowski, Janusz

Abstract

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined = 4.09 × 10−9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13–1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined = 2.74 × 10−10; OR = 1.14, 95% CI = 1.10–1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Published
2012

12. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Author

Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, Jankowski, Janusz, Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, and Jankowski, Janusz

Abstract

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined = 4.09 × 10−9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13–1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined = 2.74 × 10−10; OR = 1.14, 95% CI = 1.10–1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Published
2012

13. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Author

Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, Jankowski, Janusz, Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, and Jankowski, Janusz

Abstract

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined = 4.09 × 10−9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13–1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined = 2.74 × 10−10; OR = 1.14, 95% CI = 1.10–1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Published
2012

14. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Author

Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, Jankowski, Janusz, Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, and Jankowski, Janusz

Abstract

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined = 4.09 × 10−9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13–1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined = 2.74 × 10−10; OR = 1.14, 95% CI = 1.10–1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Published
2012

15. Symptoms, ill-health and quality of life in a support group of Porton Down veterans

Author

Allender, Steven, Maconochie, Noreen, Keegan, Thomas, Brooks, Claire, Fletcher, Tony, Nieuwenhuijsen, Mark J, Doyle, Pat, Carpenter, Lucy M, Venables, Katherine M, Allender, Steven, Maconochie, Noreen, Keegan, Thomas, Brooks, Claire, Fletcher, Tony, Nieuwenhuijsen, Mark J, Doyle, Pat, Carpenter, Lucy M, and Venables, Katherine M

Abstract

Background: There has been a Human Volunteer Programme at the British chemical weapons research facility at Porton Down since the First World War, in which some of the participants were exposed to chemical warfare agents. Aim: To identify any striking specific morbidity patterns in members of the Porton Down Veterans Support Group (PDVSG). Methods: A self-completed postal questionnaire was prepared including health immediately after the visits to Porton Down, subsequent diagnoses and hospital admissions, symptoms in, and after, the first 5 years after the visits, fatigue symptoms and current quality of life, measured using the SF-36. Results: Responses were received from 289 of 436 (66%). Results reported here relate to 269 male respondents of mean age 66.8 years. Sixty-six per cent reported their first visit to Porton Down in the 1950s. The most common diagnoses or hospital admissions reported were diseases of the circulatory system. In the first 5 years after their visits the most common symptoms were headache, irritability or outbursts of anger and feeling un-refreshed after sleep. In the later period, most common symptoms were fatigue, feeling un-refreshed after sleep and sleeping difficulties. Sixty-five per cent met the definition for a case of 'fatigue'. Current quality of life dimensions were consistently lower than age-specific estimates from general population samples. Conclusions: Members of the PDVSG responding to this survey reported poorer quality of life than the general population. Despite there being no clear pattern of specific morbidities, we cannot rule out ill-health being potentially associated with past experience at Porton Down.

Published
2006

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