30 results on '"Lee, KL"'
Search Results
2. Incremental prognostic value of echocardiography of left ventricular remodeling and diastolic function in STICH trial.
- Author
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Kim, K-H, She, L, Lee, KL, Dabrowski, R, Grayburn, PA, Rajda, M, Prior, DL, Desvigne-Nickens, P, Zoghbi, WA, Senni, M, Stefanelli, G, Beghi, C, Huynh, T, Velazquez, EJ, Oh, JK, Lin, G, Kim, K-H, She, L, Lee, KL, Dabrowski, R, Grayburn, PA, Rajda, M, Prior, DL, Desvigne-Nickens, P, Zoghbi, WA, Senni, M, Stefanelli, G, Beghi, C, Huynh, T, Velazquez, EJ, Oh, JK, and Lin, G
- Abstract
AIMS: We sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. METHODS AND RESULTS: The cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke. CONCLUSIONS: Echocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern.
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- 2020
3. Demonstration of High-speed Indoor Optical Wireless Communications using Few-mode Based Uniform Beam Shaping
- Author
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Li, J, Lim, C, Nirmalathas, A, O'Keefe, N, Lee, KL, Li, J, Lim, C, Nirmalathas, A, O'Keefe, N, and Lee, KL
- Abstract
A high-speed indoor optical wireless communications link using few-mode based uniform beam shaping is experimentally demonstrated. Results show that high-quality uniform beam can be realized and the BER performance can be improved significantly by combining the signals from different channels supported by different modes.
- Published
- 2020
4. Incremental prognostic value of echocardiography of left ventricular remodeling and diastolic function in STICH trial
- Author
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Kim, K, She, L, Lee, K, Dabrowski, R, Grayburn, P, Rajda, M, Prior, D, Desvigne-Nickens, P, Zoghbi, W, Senni, M, Stefanelli, G, Beghi, C, Huynh, T, Velazquez, E, Oh, J, Lin, G, Kim KH, She L, Lee KL, Dabrowski R, Grayburn PA, Rajda M, Prior DL, Desvigne-Nickens P, Zoghbi WA, Senni M, Stefanelli G, Beghi C, Huynh T, Velazquez EJ, Oh JK, Lin G, Kim, K, She, L, Lee, K, Dabrowski, R, Grayburn, P, Rajda, M, Prior, D, Desvigne-Nickens, P, Zoghbi, W, Senni, M, Stefanelli, G, Beghi, C, Huynh, T, Velazquez, E, Oh, J, Lin, G, Kim KH, She L, Lee KL, Dabrowski R, Grayburn PA, Rajda M, Prior DL, Desvigne-Nickens P, Zoghbi WA, Senni M, Stefanelli G, Beghi C, Huynh T, Velazquez EJ, Oh JK, and Lin G
- Abstract
Aims: We sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Methods and results: The cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke. Conclusions: Echocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern.
- Published
- 2020
5. CABG Improves Outcomes in Patients With Ischemic Cardiomyopathy: 10-Year Follow-Up of the STICH Trial
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Howlett, J, Stebbins, A, Petrie, M, Jhund, P, Castelvecchio, S, Cherniavsky, A, Sueta, C, Roy, A, Piña, I, Wurm, R, Drazner, M, Andersson, B, Batlle, C, Senni, M, Chrzanowski, L, Merkely, B, Carson, P, Desvigne-Nickens, P, Lee, K, Velazquez, E, Al-Khalidi, H, STICH Trial, I, Howlett JG, Stebbins A, Petrie MC, Jhund PS, Castelvecchio S, Cherniavsky A, Sueta CA, Roy A, Piña IL, Wurm R, Drazner MH, Andersson B, Batlle C, Senni M, Chrzanowski L, Merkely B, Carson P, Desvigne-Nickens PM, Lee KL, Velazquez EJ, Al-Khalidi HR, STICH Trial Investigators, Howlett, J, Stebbins, A, Petrie, M, Jhund, P, Castelvecchio, S, Cherniavsky, A, Sueta, C, Roy, A, Piña, I, Wurm, R, Drazner, M, Andersson, B, Batlle, C, Senni, M, Chrzanowski, L, Merkely, B, Carson, P, Desvigne-Nickens, P, Lee, K, Velazquez, E, Al-Khalidi, H, STICH Trial, I, Howlett JG, Stebbins A, Petrie MC, Jhund PS, Castelvecchio S, Cherniavsky A, Sueta CA, Roy A, Piña IL, Wurm R, Drazner MH, Andersson B, Batlle C, Senni M, Chrzanowski L, Merkely B, Carson P, Desvigne-Nickens PM, Lee KL, Velazquez EJ, Al-Khalidi HR, and STICH Trial Investigators
- Abstract
Objectives: The authors investigated the impact of coronary artery bypass grafting (CABG) on first and recurrent hospitalization in this population. Background: In the STICH (Surgical Treatment for Ischemic Heart Failure) trial, CABG reduced all-cause death and hospitalization in patients with and ischemic cardiomyopathy and left ventricular ejection fraction <35%. Methods: A total of 1,212 patients were randomized (610 to CABG + optimal medical therapy [CABG] and 602 to optimal medical therapy alone [MED] alone) and followed for a median of 9.8 years. All-cause and cause-specific hospitalizations were analyzed as time-to-first-event and as recurrent event analysis. Results: Of the 1,212 patients, 757 died (62.4%) and 732 (60.4%) were hospitalized at least once, for a total of 2,549 total all-cause hospitalizations. Most hospitalizations (66.2%) were for cardiovascular causes, of which approximately one-half (907 or 52.9%) were for heart failure. More than 70% of all hospitalizations (1,817 or 71.3%) were recurrent events. The CABG group experienced fewer all-cause hospitalizations in the time-to-first-event (349 CABG vs. 383 MED, adjusted hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.03) and in recurrent event analyses (1,199 CABG vs. 1,350 MED, HR: 0.78, 95% CI: 0.65 to 0.94; p < 0.001). This was driven by fewer total cardiovascular (CV) hospitalizations (744 vs. 968; p < 0.001, adjusted HR: 0.66, 95% CI: 0.55 to 0.81; p = 0.001), the majority of which were due to HF (395 vs. 512; p < 0.001, adjusted HR: 0.68, 95% CI: 0.52-0.89; p = 0.005). We did not observe a difference in non-CV events. Conclusions: CABG reduces all-cause, CV, and HF hospitalizations in time-to-first-event and recurrent event analyses. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595)
- Published
- 2019
6. Laryngeal closure impedes non-invasive ventilation at birth
- Author
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Crawshaw, JR, Kitchen, MJ, Binder-Heschl, C, Thio, M, Wallace, MJ, Kerr, LT, Roehr, CC, Lee, KL, Buckley, GA, Davis, PG, Flemmer, A, te Pas, AB, Hooper, SB, Crawshaw, JR, Kitchen, MJ, Binder-Heschl, C, Thio, M, Wallace, MJ, Kerr, LT, Roehr, CC, Lee, KL, Buckley, GA, Davis, PG, Flemmer, A, te Pas, AB, and Hooper, SB
- Abstract
BACKGROUND: Non-invasive ventilation is sometimes unable to provide the respiratory needs of very premature infants in the delivery room. While airway obstruction is thought to be the main problem, the site of obstruction is unknown. We investigated whether closure of the larynx and epiglottis is a major site of airway obstruction. METHODS: We used phase contrast X-ray imaging to visualise laryngeal function in spontaneously breathing premature rabbits immediately after birth and at approximately 1 hour after birth. Non-invasive respiratory support was applied via a facemask and images were analysed to determine the percentage of the time the glottis and the epiglottis were open. HYPOTHESIS: Immediately after birth, the larynx is predominantly closed, only opening briefly during a breath, making non-invasive intermittent positive pressure ventilation (iPPV) ineffective, whereas after lung aeration, the larynx is predominantly open allowing non-invasive iPPV to ventilate the lung. RESULTS: The larynx and epiglottis were predominantly closed (open 25.5%±1.1% and 17.1%±1.6% of the time, respectively) in pups with unaerated lungs and unstable breathing patterns immediately after birth. In contrast, the larynx and the epiglottis were mostly open (90.5%±1.9% and 72.3%±2.3% of the time, respectively) in pups with aerated lungs and stable breathing patterns irrespective of time after birth. CONCLUSION: Laryngeal closure impedes non-invasive iPPV at birth and may reduce the effectiveness of non-invasive respiratory support in premature infants immediately after birth.
- Published
- 2018
7. Low-power current-equalised optical transmitter for below-threshold-biasing VCSEL operation
- Author
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LI, J, Lee, KL, Chow, HK, Hinton, K, LI, J, Lee, KL, Chow, HK, and Hinton, K
- Published
- 2015
8. A 'Power-on-demand' optical transceiver design for green access and in-home network applications
- Author
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LI, J, Lee, KL, Chow, HK, LI, J, Lee, KL, and Chow, HK
- Published
- 2015
9. PIAS4 is an activator of hypoxia signalling via VHL suppression during growth of pancreatic cancer cells.
- Author
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Chien, W, Chien, W, Lee, KL, Ding, LW, Wuensche, P, Kato, H, Doan, NB, Poellinger, L, Said, JW, Koeffler, HP, Chien, W, Chien, W, Lee, KL, Ding, LW, Wuensche, P, Kato, H, Doan, NB, Poellinger, L, Said, JW, and Koeffler, HP
- Abstract
BackgroundThe PIAS4 protein belongs to the family of protein inhibitors of activated STAT, but has since been implicated in various biological activities including the post-translational modification known as sumoylation. In this study, we explored the roles of PIAS4 in pancreatic tumourigenesis.MethodsThe expression levels of PIAS4 in pancreatic cancer cells were examined. Cell proliferation and invasion was studied after overexpression and gene silencing of PIAS4. The effect of PIAS4 on hypoxia signalling was investigated.ResultsThe protein was overexpressed in pancreatic cancer cells compared with the normal pancreas. Gene silencing by PIAS4 small interfering RNA (siRNA) suppressed pancreatic cancer cell growth and overexpression of PIAS4 induced expression of genes related to cell growth. The overexpression of PIAS4 is essential for the regulation of the hypoxia signalling pathway. PIAS4 interacts with the tumour suppressor von Hippel-Lindau (VHL) and leads to VHL sumoylation, oligomerization, and impaired function. Pancreatic cancer cells (Panc0327, MiaPaCa2) treated with PIAS4 siRNA suppressed expression of the hypoxia-inducible factor hypoxia-inducible factor 1 alpha and its target genes JMJD1A, VEGF, and STAT3.ConclusionOur study elucidates the role of PIAS4 in the regulation of pancreatic cancer cell growth, where the suppression of its activity represents a novel therapeutic target for pancreatic cancers.
- Published
- 2013
10. PIAS4 is an activator of hypoxia signalling via VHL suppression during growth of pancreatic cancer cells.
- Author
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Chien, W, Chien, W, Lee, KL, Ding, LW, Wuensche, P, Kato, H, Doan, NB, Poellinger, L, Said, JW, Koeffler, HP, Chien, W, Chien, W, Lee, KL, Ding, LW, Wuensche, P, Kato, H, Doan, NB, Poellinger, L, Said, JW, and Koeffler, HP
- Abstract
BackgroundThe PIAS4 protein belongs to the family of protein inhibitors of activated STAT, but has since been implicated in various biological activities including the post-translational modification known as sumoylation. In this study, we explored the roles of PIAS4 in pancreatic tumourigenesis.MethodsThe expression levels of PIAS4 in pancreatic cancer cells were examined. Cell proliferation and invasion was studied after overexpression and gene silencing of PIAS4. The effect of PIAS4 on hypoxia signalling was investigated.ResultsThe protein was overexpressed in pancreatic cancer cells compared with the normal pancreas. Gene silencing by PIAS4 small interfering RNA (siRNA) suppressed pancreatic cancer cell growth and overexpression of PIAS4 induced expression of genes related to cell growth. The overexpression of PIAS4 is essential for the regulation of the hypoxia signalling pathway. PIAS4 interacts with the tumour suppressor von Hippel-Lindau (VHL) and leads to VHL sumoylation, oligomerization, and impaired function. Pancreatic cancer cells (Panc0327, MiaPaCa2) treated with PIAS4 siRNA suppressed expression of the hypoxia-inducible factor hypoxia-inducible factor 1 alpha and its target genes JMJD1A, VEGF, and STAT3.ConclusionOur study elucidates the role of PIAS4 in the regulation of pancreatic cancer cell growth, where the suppression of its activity represents a novel therapeutic target for pancreatic cancers.
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- 2013
11. Energy efficiency in future 40-Gb/s fiber access networks
- Author
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Sedighi, B, Lee, KL, Tucker, RS, Chow, H, Vetter, P, Sedighi, B, Lee, KL, Tucker, RS, Chow, H, and Vetter, P
- Published
- 2012
12. Influence of Mitral Regurgitation Repair on Survival in the Surgical Treatment for Ischemic Heart Failure Trial
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Deja, M, Grayburn, P, Sun, B, Rao, V, She, L, Krejca, M, Jain, A, Chua, Y, Daly, R, Senni, M, Mokrzycki, K, Menicanti, L, Oh, J, Michler, R, Wrobel, K, Lamy, A, Velazquez, E, Lee, K, Jones, R, Deja MA, Grayburn PA, Sun B, Rao V, She LL, Krejca M, Jain AR, Chua YL, Daly R, Senni M, Mokrzycki K, Menicanti L, Oh JK, Michler R, Wrobel K, Lamy A, Velazquez EJ, Lee KL, Jones RH, Deja, M, Grayburn, P, Sun, B, Rao, V, She, L, Krejca, M, Jain, A, Chua, Y, Daly, R, Senni, M, Mokrzycki, K, Menicanti, L, Oh, J, Michler, R, Wrobel, K, Lamy, A, Velazquez, E, Lee, K, Jones, R, Deja MA, Grayburn PA, Sun B, Rao V, She LL, Krejca M, Jain AR, Chua YL, Daly R, Senni M, Mokrzycki K, Menicanti L, Oh JK, Michler R, Wrobel K, Lamy A, Velazquez EJ, Lee KL, and Jones RH
- Abstract
Background-Whether mitral valve repair during coronary artery bypass grafting (CABG) improves survival in patients with ischemic mitral regurgitation (MR) remains unknown. Methods and Results-Patients with ejection fraction ≤35% and coronary artery disease amenable to CABG were randomized at 99 sites worldwide to medical therapy with or without CABG. The decision to treat the mitral valve during CABG was left to the surgeon. The primary end point was mortality. Of 1212 randomized patients, 435 (36%) had none/trace MR, 554 (46%) had mild MR, 181 (15%) had moderate MR, and 39 (3%) had severe MR. In the medical arm, 70 deaths (32%) occurred in patients with none/trace MR, 114 (44%) in those with mild MR, and 58 (50%) in those with moderate to severe MR. In patients with moderate to severe MR, there were 29 deaths (53%) among 55 patients randomized to CABG who did not receive mitral surgery (hazard ratio versus medical therapy, 1.20; 95% confidence interval, 0.77-1.87) and 21 deaths (43%) among 49 patients who received mitral surgery (hazard ratio versus medical therapy, 0.62; 95% confidence interval, 0.35-1.08). After adjustment for baseline prognostic variables, the hazard ratio for CABG with mitral surgery versus CABG alone was 0.41 (95% confidence interval, 0.22-0.77; P=0.006). Conclusion-Although these observational data suggest that adding mitral valve repair to CABG in patients with left ventricular dysfunction and moderate to severe MR may improve survival compared with CABG alone or medical therapy alone, a prospective randomized trial is necessary to confirm the validity of these observations. Clinical Trial Registration-URL: http://www.clinicaltrials. gov. Unique identifier: NCT00023595.
- Published
- 2012
13. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
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Craddock, N, Hurles, ME, Cardin, N, Pearson, RD, Plagnol, V, Robson, S, Vukcevic, D, Barnes, C, Conrad, DF, Giannoulatou, E, Holmes, C, Marchini, JL, Stirrups, K, Tobin, MD, Wain, LV, Yau, C, Aerts, J, Ahmad, T, Andrews, TD, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Clee, CM, Coffey, AJ, Connell, JMC, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Feuk, L, Fitzgerald, T, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Freathy, RM, Gibbs, P, Gilbert, P, Gokumen, O, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Onyiah, I, Ovington, NR, Owen, MJ, Palin, K, Parnell, K, Pernet, D, Perry, JRB, Phillips, A, Pinto, D, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Redon, R, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Schuilenburg, H, Scott, CE, Scott, R, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stone, MA, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Travers, ME, Turnbull, C, Valsesia, A, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Young, AH, Zeggini, E, Carter, NP, Frayling, TM, Lee, C, McVean, G, Munroe, PB, Palotie, A, Sawcer, SJ, Scherer, SW, Strachan, DP, Tyler-Smith, C, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, Donnelly, P, Craddock, N, Hurles, ME, Cardin, N, Pearson, RD, Plagnol, V, Robson, S, Vukcevic, D, Barnes, C, Conrad, DF, Giannoulatou, E, Holmes, C, Marchini, JL, Stirrups, K, Tobin, MD, Wain, LV, Yau, C, Aerts, J, Ahmad, T, Andrews, TD, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Clee, CM, Coffey, AJ, Connell, JMC, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Feuk, L, Fitzgerald, T, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Freathy, RM, Gibbs, P, Gilbert, P, Gokumen, O, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Onyiah, I, Ovington, NR, Owen, MJ, Palin, K, Parnell, K, Pernet, D, Perry, JRB, Phillips, A, Pinto, D, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Redon, R, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Schuilenburg, H, Scott, CE, Scott, R, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stone, MA, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Travers, ME, Turnbull, C, Valsesia, A, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Young, AH, Zeggini, E, Carter, NP, Frayling, TM, Lee, C, McVean, G, Munroe, PB, Palotie, A, Sawcer, SJ, Scherer, SW, Strachan, DP, Tyler-Smith, C, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, and Donnelly, P
- Abstract
Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
- Published
- 2010
14. Extended-reach gigabit passive optical network for rural areas using distributed Raman amplifiers
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Lee, KL, Riding, JL, Tran, AV, Tucker, RS, Lee, KL, Riding, JL, Tran, AV, and Tucker, RS
- Published
- 2009
15. Simplified base station configuration for fiber-wireless applications
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Wong, E, Lim, C, Prasanna, AG, Lee, KL, Nirmalathas, A, Ortsiefer, M, Neumeyr, C, Wong, E, Lim, C, Prasanna, AG, Lee, KL, Nirmalathas, A, Ortsiefer, M, and Neumeyr, C
- Published
- 2007
16. Optical interface for IMD reduction in fiber-radio systems with simultaneous baseband transmission for heterogeneous access networks
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Lim, C, Lee, KL, Nirmalathas, A, Novak, D, Waterhouse, R, Lim, C, Lee, KL, Nirmalathas, A, Novak, D, and Waterhouse, R
- Published
- 2007
17. Analysis of mercury in Malaysian herbal preparations
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Ang, HH, Lee, KL, Ang, HH, and Lee, KL
- Abstract
The DCA (Drug Control Authority) in Malaysia started implementing the phase three registration of traditional medicines on 1st January 1992 with special emphasis on the quality, efficacy and safety in all pharmaceutical dosage forms of traditional medicinal preparations. The rhizome of Smilax luzonensis is eaten as an aphrodisiac in the Malaysian community. This study was conducted to analyse the mercury content of 100 pharmaceutical dosage forms of S. luzonensis that were purchased in the Malaysian market, using cold vapour atomic absorption spectrophotometer. Results show that 86% of the products complied with the quality requirement for traditional medicinal preparations in Malaysia with particular reference to mercury content. Mercury, which has adverse effect on the male reproductive system, is present in 14% of the products examined, which calls for urgent action by the Malaysian government towards rectifying the abnormality.
- Published
- 2006
18. Directly-modulated self-seeding reflective soas in WDM-PONs: Performance dependence on seeding power and modulation effects
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Lee, KL, Wong, E, Lee, KL, and Wong, E
- Published
- 2006
19. Polarization and bit-length independent all-optical logic gate based active correlator for bit serial label processing
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Gopalakrishnapillai, BS, Lee, KL, Nirmalathas, A, Lim, C, Shinada, S, Wada, N, Miyazaki, T, Gopalakrishnapillai, BS, Lee, KL, Nirmalathas, A, Lim, C, Shinada, S, Wada, N, and Miyazaki, T
- Published
- 2006
20. Directly-modulated self-seeding reflective SOAs as colorless transmitters for WDM passive optical networks
- Author
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Wong, E, Lee, KL, Anderson, T, Wong, E, Lee, KL, and Anderson, T
- Published
- 2006
21. Analysis of mercury in Malaysian herbal preparations
- Author
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Ang, HH, Lee, KL, Ang, HH, and Lee, KL
- Abstract
The DCA (Drug Control Authority) in Malaysia started implementing the phase three registration of traditional medicines on 1st January 1992 with special emphasis on the quality, efficacy and safety in all pharmaceutical dosage forms of traditional medicinal preparations. The rhizome of Smilax luzonensis is eaten as an aphrodisiac in the Malaysian community. This study was conducted to analyse the mercury content of 100 pharmaceutical dosage forms of S. luzonensis that were purchased in the Malaysian market, using cold vapour atomic absorption spectrophotometer. Results show that 86% of the products complied with the quality requirement for traditional medicinal preparations in Malaysia with particular reference to mercury content. Mercury, which has adverse effect on the male reproductive system, is present in 14% of the products examined, which calls for urgent action by the Malaysian government towards rectifying the abnormality.
- Published
- 2006
22. Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation - Incidence, predictors, and outcomes
- Author
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Al-Khatib, SM, Granger, CB, Huang, Y, Lee, KL, Califf, RM, Simoons, Maarten, Armstrong, PW, van der Werf, F, White, HD, Simes, RJ, Moliterno, DJ, Topol, EJ, Harrington, RA, Al-Khatib, SM, Granger, CB, Huang, Y, Lee, KL, Califf, RM, Simoons, Maarten, Armstrong, PW, van der Werf, F, White, HD, Simes, RJ, Moliterno, DJ, Topol, EJ, and Harrington, RA
- Published
- 2002
23. Systematic adjudication of myocardial infarction end-points in an international clinical trial
- Author
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Mahaffey, KW, Harrington, RA, Akkerhuis, Martijn, Kleiman, NS, Berdan, LG, Crenshaw, BS, Tardiff, BE, Granger, CB, DeJong, I, Bhapkar, M, Widimsky, P, Corbalon, R, Lee, KL, Deckers, Jaap, Simoons, Maarten, Topol, EJ, Califf, RM, PURSUIT Investigators,, Mahaffey, KW, Harrington, RA, Akkerhuis, Martijn, Kleiman, NS, Berdan, LG, Crenshaw, BS, Tardiff, BE, Granger, CB, DeJong, I, Bhapkar, M, Widimsky, P, Corbalon, R, Lee, KL, Deckers, Jaap, Simoons, Maarten, Topol, EJ, Califf, RM, and PURSUIT Investigators,
- Published
- 2001
24. Disagreements between central clinical events committee and site investigator assessments of myocardial infarction endpoints in an international clinical trial: review of the PURSUIT study
- Author
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Mahaffey, KW, Harrington, RA, Akkerhuis, Martijn, Kleiman, NS, Berdan, LG, Crenshaw, BS, Tardiff, BE, Granger, CB, DeJong, I, Bhapkar, M, Widimsky, P, Corbalon, R, Lee, KL, Deckers, Jaap, Simoons, Maarten, Topol, EJ, Califf, RM, PURSUIT Investigators,, Mahaffey, KW, Harrington, RA, Akkerhuis, Martijn, Kleiman, NS, Berdan, LG, Crenshaw, BS, Tardiff, BE, Granger, CB, DeJong, I, Bhapkar, M, Widimsky, P, Corbalon, R, Lee, KL, Deckers, Jaap, Simoons, Maarten, Topol, EJ, Califf, RM, and PURSUIT Investigators,
- Published
- 2001
25. Perspectives on Large-Scale Cardiavascular Clinical Trials for the New Millenium.
- Author
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Topol, EJ, Califf, RM, van der Werf, F, Simoons, Maarten, Hampton, J, Lee, KL, White, HD, Simes, J, Armstrong, PW, Topol, EJ, Califf, RM, van der Werf, F, Simoons, Maarten, Hampton, J, Lee, KL, White, HD, Simes, J, and Armstrong, PW
- Published
- 1997
26. Incidence and predictors of bleeding after comtemporary thrombolytic therapy for myocardial infarction.
- Author
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Berkowitz, SC, Granger, CB, Pieper, KS, Lee, KL, Gore, JM, Simoons, Maarten, Berkowitz, SC, Granger, CB, Pieper, KS, Lee, KL, Gore, JM, and Simoons, Maarten
- Published
- 1997
27. Selection of thrombolytic therapy for individual patients: development of a clinical model.
- Author
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Califf, RM, Woodlief, LH, Harrell, FE, Lee, KL, White, HD, Guerci, A, Barbash, GI, Simes, J, Weaver, WD, Simoons, Maarten, Califf, RM, Woodlief, LH, Harrell, FE, Lee, KL, White, HD, Guerci, A, Barbash, GI, Simes, J, Weaver, WD, and Simoons, Maarten
- Published
- 1997
28. Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: Results for the GUSTO-I trial
- Author
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UCL, Granger, CB, Hirsh, J, Califf, RM., Col, Jacques, White, HD, Betriu, A., Woodlief, LH., Lee, KL., Bovill, EG, Simes, J, Topol, EJ., UCL, Granger, CB, Hirsh, J, Califf, RM., Col, Jacques, White, HD, Betriu, A., Woodlief, LH., Lee, KL., Bovill, EG, Simes, J, and Topol, EJ.
- Abstract
Background Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29 656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. Methods and Results Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P<.00001) as well as older age, female sex, and lack of cigarette smoking (all P<.0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rater; was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of rt infarction in the first 10 hours after discontinuation of intravenous heparin. Conclusions Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should oo consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.
- Published
- 1996
29. Predictors of 30-day Mortality in the Era of Reperfusion for Acute Myocardial-infarction - Results From An International Trial of 41 021 Patients
- Author
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UCL, Lee, KL., Woodlief, LH., Topol, EJ., Weaver, WD., Betriu, A., Col, Jacques, Simoons, M., Aylward, P., Vandewerf, F., Califf, RM., UCL, Lee, KL., Woodlief, LH., Topol, EJ., Weaver, WD., Betriu, A., Col, Jacques, Simoons, M., Aylward, P., Vandewerf, F., and Califf, RM.
- Abstract
Background Despite remarkable advances in the treatment of acute myocardial infarction, substantial early patient mortality remains. Appropriate choices among alternative therapies and the use of clinical resources depend on an estimate of the patient's risk. Individual patients reflect a combination of clinical features that influence prognosis, and these factors must be appropriately weighted to produce an accurate assessment of risk. Prior studies to define prognosis either were performed before widespread use of thrombolysis or were limited in sample size or spectrum of data. Using the large population of the GUSTO-I trial, we performed a comprehensive analysis of relations between baseline clinical data and 30-day mortality and developed a multivariable statistical model for risk assessment in candidates for thrombolytic therapy. Methods and Results For the 41 021 patients enrolled in GUSTO-I, a randomized trial of four thrombolytic strategies, relations between clinical descriptors routinely collected at initial presentation, and death within 30 days (which occurred in 7% of the population) were examined with both univariable and multivariable analyses. Variables studied included demographics, history and risk factors, presenting characteristics, and treatment assignment. Risk modeling was performed with logistic multiple regression and validated with bootstrapping techniques. Multivariable analysis identified age as the most significant factor influencing 30-day mortality, with rates of 1.1% in the youngest decile (<45 years) and 20.5% in patients >75 (adjusted chi(2)=717, P<.0001). Other factors most significantly associated with increased mortality were lower systolic blood pressure (chi(2)=550, P<.0001), higher Killip class (chi(2)=350, P<.0001), elevated heart rate (chi(2)=275, P<.0001), and anterior infarction (chi(2)=143, P<.0001). Together, these five characteristics contained 90% of the prognostic information in the baseline clinical data. Other signi
- Published
- 1995
30. Genome-wide association study identifies eight loci associated with blood pressure
- Author
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Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K, Nilsson, P, Van Der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliot, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, De Jong, PE, Snieder, H, Van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Altshuler, D, Jarvelin, M, Elliott, P, Lakatta, EG, Forouhi, N, Wareham, NJ, Loos, RJF, Deloukas, P, Lathrop, GM, Zelenika, D, Strachan, DP, Soranzo, N, Williams, FM, Zhai, G, Spector, TD, Peden, JF, Watkins, H, Ferrucci, L, Caulfield, M, Munroe, PB, Berglund, G, Melander, O, Matullo, G, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Ernst, F, Homuth, G, Völker, U, Elosua, R, Laakso, M, Connell, JM, Mooser, V, Salomaa, V, Tuomilehto, J, Laan, M, Navis, G, Seedorf, U, Syvänen, A, Tognoni, G, Sanna, S, Uda, M, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Felix, SB, Reffelmann, T, Lorbeer, R, Völzke, H, Rettig, R, Galan, P, Hercberg, S, Bingham, SA, Kooner, JS, Bandinelli, S, Meneton, P, Abecasis, G, Thompson, JR, Braga Marcano, CA, Barke, B, Dobson, R, Gungadoo, J, Lee, KL, Onipinla, A, Wallace, I, Xue, M, Clayton, DG, Leung, H, Nutland, S, Walker, NM, Todd, JA, Stevens, HE, Dunger, DB, Widmer, B, Downes, K, Cardon, LR, Kwiatkowski, DP, Barrett, JC, Evans, D, Morris, AP, Lindgren, CM, Rayner, NW, Timpson, NJ, Lyons, E, Vannberg, F, Hill, AVS, Teo, YY, Rockett, KA, Craddock, N, Attwood, AP, Bryan, C, Bumpstead, SJ, Chaney, A, Ghori, J, William, RG, Hunt, SE, Inouye, M, Keniry, E, King, E, McGinnis, R, Potter, S, Ravindrarajan, R, Whittaker, P, Withers, D, Bentley, D, Groves, CJ, Duncanson, A, Ouwehand, WH, Boorman, JP, Cant, B, Jolley, JD, Knight, AS, Koch, K, Taylor, NC, Watkins, NA, Winzer, T, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Donnely, P, Davidson, D, Marchini, JL, Spencer, ICA, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, IB, Howie, BN, Su, Z, Vukcevic, D, Easton, D, Everson, U, Hussey, JM, Meech, E, Prowse, CV, Walters, GR, Jones, RW, Ring, SM, Prembey, M, Breen, G, St Clair, D, Ceasar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskovina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGruffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, DT, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Lewis, CM, Onnie, CM, Prescott, NJ, Mathew, CG, Forbes, A, Sanderson, J, Mathew, C, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hider, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DPM, Thomson, W, Worthington, J, Frayling, TM, Freathy, RM, Lango, H, Perry, JRB, Weedon, MN, Hattersley, AT, Shields, BM, Hitman, GA, Walker, M, Newport, M, Sirugo, G, Conway, D, Jallow, M, Bradbury, LA, Pointon, JL, Brown, MA, Farrar, C, Wordsworth, P, Franklyn, JA, Heward, JM, Simmonds, MJ, Cough, SCL, Seal, S, Stratton, MR, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K, Nilsson, P, Van Der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliot, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, De Jong, PE, Snieder, H, Van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Altshuler, D, Jarvelin, M, Elliott, P, Lakatta, EG, Forouhi, N, Wareham, NJ, Loos, RJF, Deloukas, P, Lathrop, GM, Zelenika, D, Strachan, DP, Soranzo, N, Williams, FM, Zhai, G, Spector, TD, Peden, JF, Watkins, H, Ferrucci, L, Caulfield, M, Munroe, PB, Berglund, G, Melander, O, Matullo, G, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Ernst, F, Homuth, G, Völker, U, Elosua, R, Laakso, M, Connell, JM, Mooser, V, Salomaa, V, Tuomilehto, J, Laan, M, Navis, G, Seedorf, U, Syvänen, A, Tognoni, G, Sanna, S, Uda, M, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Felix, SB, Reffelmann, T, Lorbeer, R, Völzke, H, Rettig, R, Galan, P, Hercberg, S, Bingham, SA, Kooner, JS, Bandinelli, S, Meneton, P, Abecasis, G, Thompson, JR, Braga Marcano, CA, Barke, B, Dobson, R, Gungadoo, J, Lee, KL, Onipinla, A, Wallace, I, Xue, M, Clayton, DG, Leung, H, Nutland, S, Walker, NM, Todd, JA, Stevens, HE, Dunger, DB, Widmer, B, Downes, K, Cardon, LR, Kwiatkowski, DP, Barrett, JC, Evans, D, Morris, AP, Lindgren, CM, Rayner, NW, Timpson, NJ, Lyons, E, Vannberg, F, Hill, AVS, Teo, YY, Rockett, KA, Craddock, N, Attwood, AP, Bryan, C, Bumpstead, SJ, Chaney, A, Ghori, J, William, RG, Hunt, SE, Inouye, M, Keniry, E, King, E, McGinnis, R, Potter, S, Ravindrarajan, R, Whittaker, P, Withers, D, Bentley, D, Groves, CJ, Duncanson, A, Ouwehand, WH, Boorman, JP, Cant, B, Jolley, JD, Knight, AS, Koch, K, Taylor, NC, Watkins, NA, Winzer, T, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Donnely, P, Davidson, D, Marchini, JL, Spencer, ICA, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, IB, Howie, BN, Su, Z, Vukcevic, D, Easton, D, Everson, U, Hussey, JM, Meech, E, Prowse, CV, Walters, GR, Jones, RW, Ring, SM, Prembey, M, Breen, G, St Clair, D, Ceasar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskovina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGruffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, DT, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Lewis, CM, Onnie, CM, Prescott, NJ, Mathew, CG, Forbes, A, Sanderson, J, Mathew, C, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hider, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DPM, Thomson, W, Worthington, J, Frayling, TM, Freathy, RM, Lango, H, Perry, JRB, Weedon, MN, Hattersley, AT, Shields, BM, Hitman, GA, Walker, M, Newport, M, Sirugo, G, Conway, D, Jallow, M, Bradbury, LA, Pointon, JL, Brown, MA, Farrar, C, Wordsworth, P, Franklyn, JA, Heward, JM, Simmonds, MJ, Cough, SCL, Seal, S, Stratton, MR, Ban, M, Goris, A, Sawcer, SJ, and Compston, A
- Abstract
Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10−24), CYP1A2 (P = 1 × 10−23), FGF5 (P = 1 × 10−21), SH2B3 (P = 3 × 10−18), MTHFR (P = 2 × 10−13), c10orf107 (P = 1 × 10−9), ZNF652 (P = 5 × 10−9) and PLCD3 (P = 1 × 10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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