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111 results on '"Witte, D"'

1. Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: a randomised, double-blind, four-arm parallel group dose-ranging study

Author: Witte, D, Handley, A, Jere, KC, Bogandovic-Sakran, N, Mpakiza, A, Turner, A, Pavlic, D, Boniface, K, Mandolo, J, Ong, DS, Bonnici, R, Justice, F, Bar-Zeev, N, Iturriza-Gomara, M, Ackland, J, Donato, CM, Cowley, D, Barnes, G, Cunliffe, NA, Bines, JE, Witte, D, Handley, A, Jere, KC, Bogandovic-Sakran, N, Mpakiza, A, Turner, A, Pavlic, D, Boniface, K, Mandolo, J, Ong, DS, Bonnici, R, Justice, F, Bar-Zeev, N, Iturriza-Gomara, M, Ackland, J, Donato, CM, Cowley, D, Barnes, G, Cunliffe, NA, and Bines, JE
Abstract: BACKGROUND: Rotavirus vaccines reduce rotavirus-related deaths and hospitalisations but are less effective in high child mortality countries. The human RV3-BB neonatal G3P[6] rotavirus vaccine administered in a neonatal schedule was efficacious in reducing severe rotavirus gastroenteritis in Indonesia but had not yet been evaluated in African infants. METHODS: We did a phase 2, randomised, double-blind, parallel group dose-ranging study of three doses of oral RV3-BB rotavirus vaccine in infants in three primary health centres in Blantyre, Malawi. Healthy infants less than 6 days of age with a birthweight 2·5 to 4·0 kg were randomly assigned (1:1:1:1) into one of four treatment groups: neonatal vaccine group, which included high-titre (1·0 × 107 focus-forming unit [FFU] per mL), mid-titre (3·0 × 106 FFU per mL), or low-titre (1·0 × 106 FFU per mL); and infant vaccine group, which included high-titre (1·0 × 107 FFU per mL) using a computer generated code (block size of four), stratified by birth (singleton vs multiple). Neonates received their three doses at 0-5 days to 10 weeks and infants at 6-14 weeks. Investigators, participant families, and laboratory staff were masked to group allocation. Anti-rotavirus IgA seroconversion and vaccine take (IgA seroconversion and stool shedding) were evaluated. Safety was assessed in all participants who received at least one dose of vaccine or placebo. The primary outcome was the cumulative IgA seroconversion 4 weeks after three doses of RV3-BB in the neonatal schedule in the high-titre, mid-titre, and low-titre groups in the per protocol population, with its 95% CI. With the high-titre group as the active control group, we did a non-inferiority analysis of the proportion of participants with IgA seroconversion in the mid-titre and low-titre groups, using a non-inferiority margin of less than 20%. This trial is registered at ClinicalTrials.gov (NCT03483116). FINDINGS: Between Sept 17, 2018, and Jan 27, 2020, 711 participants rec
Published: 2022

2. Prevalence of peripheral and cardiovascular autonomic neuropathy in Greenlanders with diabetes and prediabetes based on national normative reference data

Author: Christensen, M. M. B., Hansen, C. S., Vistisen, D., Fleischer, J., Witte, D. R., Jørgensen, M. E., Christensen, M. M. B., Hansen, C. S., Vistisen, D., Fleischer, J., Witte, D. R., and Jørgensen, M. E.
Published: 2022

3. Combined Airborne Wind and Photovoltaic Energy System for Martian Habitats

Author: Ouroumova, L.H. (author), Witte, D. (author), Klootwijk, B.J. (author), Terwindt, E.N. (author), van Marion, F. (author), Mordasov, D. (author), Corte Vargas, F. (author), Heidweiller, S. (author), Géczi, M. (author), Kempers, M.X. (author), Schmehl, R. (author), Ouroumova, L.H. (author), Witte, D. (author), Klootwijk, B.J. (author), Terwindt, E.N. (author), van Marion, F. (author), Mordasov, D. (author), Corte Vargas, F. (author), Heidweiller, S. (author), Géczi, M. (author), Kempers, M.X. (author), and Schmehl, R. (author)
Abstract: Generating renewable energy on Mars is technologically challenging. Firstly, because, compared to Earth, key energy resources such as solar and wind are weak as a result of very low atmospheric pressure and low solar irradiation. Secondly, because of the harsh environmental conditions, the required high degree of automation, and the exceptional effort and cost involved in transporting material to the planet. Like on Earth, it is crucial to combine complementary resources for an effective renewable energy solution. In this work, we present the results of a design synthesis exercise, a 10 kW microgrid solution, based on a pumping kite power system and photovoltaic solar modules to power the construction and subsequent use of a Mars habitat. To buffer unavoidable energy fluctuations and balance seasonal and diurnal resource variations, the two energy systems are combined with a compressed gas storage system and lithium-sulphur batteries. The airborne wind energy solution was selected because of its low weight-to-wing-surface-area ratio, compact packing volume, and high capacity factor which enables it to endure strong dust storms in an airborne parking mode. The surface area of the membrane wing is 50 m2 and the mass of the entire system, including the kite control unit and ground station, is 290 kg. The performance of the microgrid was assessed by computational simulation using available resource data for a chosen deployment location on Mars. The projected costs of the system are €8.95 million, excluding transportation to Mars., Wind Energy
Published: 2021
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4. Combined Airborne Wind and Photovoltaic Energy System for Martian Habitats

Author: Ouroumova, L.H. (author), Witte, D. (author), Klootwijk, B.J. (author), Terwindt, E.N. (author), van Marion, F. (author), Mordasov, D. (author), Corte Vargas, F. (author), Heidweiller, S. (author), Géczi, M. (author), Kempers, M.X. (author), Schmehl, R. (author), Ouroumova, L.H. (author), Witte, D. (author), Klootwijk, B.J. (author), Terwindt, E.N. (author), van Marion, F. (author), Mordasov, D. (author), Corte Vargas, F. (author), Heidweiller, S. (author), Géczi, M. (author), Kempers, M.X. (author), and Schmehl, R. (author)
Abstract: Generating renewable energy on Mars is technologically challenging. Firstly, because, compared to Earth, key energy resources such as solar and wind are weak as a result of very low atmospheric pressure and low solar irradiation. Secondly, because of the harsh environmental conditions, the required high degree of automation, and the exceptional effort and cost involved in transporting material to the planet. Like on Earth, it is crucial to combine complementary resources for an effective renewable energy solution. In this work, we present the results of a design synthesis exercise, a 10 kW microgrid solution, based on a pumping kite power system and photovoltaic solar modules to power the construction and subsequent use of a Mars habitat. To buffer unavoidable energy fluctuations and balance seasonal and diurnal resource variations, the two energy systems are combined with a compressed gas storage system and lithium-sulphur batteries. The airborne wind energy solution was selected because of its low weight-to-wing-surface-area ratio, compact packing volume, and high capacity factor which enables it to endure strong dust storms in an airborne parking mode. The surface area of the membrane wing is 50 m2 and the mass of the entire system, including the kite control unit and ground station, is 290 kg. The performance of the microgrid was assessed by computational simulation using available resource data for a chosen deployment location on Mars. The projected costs of the system are €8.95 million, excluding transportation to Mars., Wind Energy
Published: 2021
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5. Improvement of Cardiac Function After Roux-en-Y Gastric Bypass in Morbidly Obese Patients Without Cardiac History Measured by Cardiac MRI

Author: de Witte, D. (Dennis), Wijngaarden, L.H. (Leontine), Houten, V.A.A. (Vera) van, Dorpel, M.A. (Marinus) van den, Bruning, T. (Tobias), Harst, E. (Erwin) van der, Klaassen, R.A. (René), Niezen, R.A., de Witte, D. (Dennis), Wijngaarden, L.H. (Leontine), Houten, V.A.A. (Vera) van, Dorpel, M.A. (Marinus) van den, Bruning, T. (Tobias), Harst, E. (Erwin) van der, Klaassen, R.A. (René), and Niezen, R.A.
Abstract: Purpose: Metabolic syndrome in patients with morbid obesity causes a higher cardiovascular morbidity, eventually leading to left ventricular hypertrophy and decreased left ventricular ejection fraction (LVEF). Roux-en-Y gastric bypass (RYGB) is considered the gold standard modality for treatment of morbid obesity and might even lead to improved cardiac function. Our objective is to investigate whether cardiac function in patients with morbid obesity improves after RYGB. Materials and Methods: In this single center pilot study, 15 patients with an uneventful cardiac history who underwent RYGB were included from May 2015 to March 2016. Cardiac function was measured by cardiac magnetic resonance imaging (CMRI), performed preoperatively and 3, 6, and 12 months postoperative. LVEF and myocardial mass and cardiac output were measured. Results: A total of 13 patients without decreased LVEF preoperative completed follow-up (mean age 37, 48.0 ± 8.8). There was a significant decrease of cardiac output 12 months postoperative (8.3 ± 1.8 preoperative vs. 6.8 ± 1.8 after 12 months, P = 0.001). Average myocardial mass declined by 15.2% (P < 0.001). After correction for body surface area (BSA), this appeared to be non-significant (P = 0.36). There was a significant improvement of LVEF/BSA at 6 and 12 months postoperative (26.2 ± 4.1 preoperative vs. 28.4 ± 3.4 and 29.2 ± 3.6 respectively, both P = 0.002). Additionally, there was a significant improvement of stroke volume/BSA 12 months after surgery (45.8 ± 8.0 vs. 51.9 ± 10.7, P = 0.033). Conclusion: RYGB in patients with morbid obesity with uneventful history of cardiac disease leads to improvement of cardiac function.
Published: 2020
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6. Arcadian Renewable Energy System: Renewable Energy for Mars Habitat

Author: Corte Vargas, F. (author), Géczi, M. (author), Heidweiller, S. (author), Kempers, M.X. (author), Klootwijk, B.J. (author), van Marion, F. (author), Mordasov, D. (author), Ouroumova, L.H. (author), Terwindt, E.N. (author), Witte, D. (author), Corte Vargas, F. (author), Géczi, M. (author), Heidweiller, S. (author), Kempers, M.X. (author), Klootwijk, B.J. (author), van Marion, F. (author), Mordasov, D. (author), Ouroumova, L.H. (author), Terwindt, E.N. (author), and Witte, D. (author)
Abstract: The human eye has turned itself back to the sky with the commercialisation of the space industry, and a new goal has been set. Setting foot on the Red Planet is the next stage of the human exploration of the universe. The travel to Mars is very lengthy and costly, nonetheless the planet still shows great potential for sustaining human life. To make this a possibility, there is a need for locally sourced energy. The presence of (re-)usable resources on Mars could pave the way to further expand the exploration to an interplanetary scale, and successfully maintain a human presence outside the Earth's atmosphere. The availability of energy will be a key indicator for the success of the human race in the colonisation of Mars. To answer this call for the need to generate locally sourced energy, the design of a renewable energy system was started by a team of students and staff from the faculty of Aerospace Engineering at Delft University of Technology: The Arcadian Renewable Energy System (ARES). The energy system will power the construction and operations of a Mars habitat, to support the livability of humans. The system will use complementary renewable energy sources integrated into a microgrid, to sustainably harvest energy from local Martian environment and resources. To ensure the design will be able to fulfil its purpose, a mission need statement and a project objective statement are generated: Mission Need Statement: To provide renewable energy supply of 10 kW to a Mars habitat. Project Objective Statement: Design a renewable energy supply system, primarily focusing on wind energy, which provides 10kW to a Mars habitat, by 10 students in 10 weeks. Synthesis Exercise (DSE) will last a total of 10 weeks, beginning on the 20th of April, ending on the 2nd of July, with a poster session and symposium. The DSE is in collaboration with the Architectural faculty, where a separate team of students is working on a rhizomatic Mars habitat project as part of an ESA competition, Aerospace Engineering
Published: 2020

7. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, P. (Praveen), Feofanova, E. V. (Elena, V), Lahrouchi, N. (Najim), Ntalla, I. (Ioanna), Karthikeyan, S. (Savita), Cook, J. (James), Chen, L. (Lingyan), Mifsud, B. (Borbala), Yao, C. (Chen), Kraja, A. T. (Aldi T.), Cartwright, J. H. (James H.), Hellwege, J. N. (Jacklyn N.), Giri, A. (Ayush), Tragante, V. (Vinicius), Thorleifsson, G. (Gudmar), Liu, D. J. (Dajiang J.), Prins, B. P. (Bram P.), Stewart, I. D. (Isobel D.), Cabrera, C. P. (Claudia P.), Eales, J. M. (James M.), Akbarov, A. (Artur), Auer, P. L. (Paul L.), Bielak, L. F. (Lawrence F.), Bis, J. C. (Joshua C.), Braithwaite, V. S. (Vickie S.), Brody, J. A. (Jennifer A.), Daw, E. W. (E. Warwick), Warren, H. R. (Helen R.), Drenos, F. (Fotios), Nielsen, S. F. (Sune Fallgaard), Faul, J. D. (Jessica D.), Fauman, E. B. (Eric B.), Fava, C. (Cristiano), Ferreira, T. (Teresa), Foley, C. N. (Christopher N.), Franceschini, N. (Nora), Gao, H. (He), Giannakopoulou, O. (Olga), Giulianini, F. (Franco), Gudbjartsson, D. F. (Daniel F.), Guo, X. (Xiuqing), Harris, S. E. (Sarah E.), Havulinna, A. S. (Aki S.), Helgadottir, A. (Anna), Huffman, J. E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Kanoni, S. (Stavroula), Kontto, J. (Jukka), Larson, M. G. (Martin G.), Li-Gao, R. (Ruifang), Lindstrom, J. (Jaana), Lotta, L. A. (Luca A.), Lu, Y. (Yingchang), Luan, J. (Jian'an), Mahajan, A. (Anubha), Malerba, G. (Giovanni), Masca, N. G. (Nicholas G. D.), Mei, H. (Hao), Menni, C. (Cristina), Mook-Kanamori, D. O. (Dennis O.), Mosen-Ansorena, D. (David), Muller-Nurasyid, M. (Martina), Pare, G. (Guillaume), Paul, D. S. (Dirk S.), Perola, M. (Markus), Poveda, A. (Alaitz), Rauramaa, R. (Rainer), Richard, M. (Melissa), Richardson, T. G. (Tom G.), Sepulveda, N. (Nuno), Sim, X. (Xueling), Smith, A. V. (Albert, V), Smith, J. A. (Jennifer A.), Staley, J. R. (James R.), Stanakova, A. (Alena), Sulem, P. (Patrick), Theriault, S. (Sebastien), Thorsteinsdottir, U. (Unnur), Trompet, S. (Stella), Varga, T. V. (Tibor V.), Edwards, D. R. (Digna R. Velez), Veronesi, G. (Giovanni), Weiss, S. (Stefan), Willems, S. M. (Sara M.), Yao, J. (Jie), Young, R. (Robin), Yu, B. (Bing), Zhang, W. (Weihua), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Evangelou, E. (Evangelos), Aeschbacher, S. (Stefanie), Asllanaj, E. (Eralda), Blankenberg, S. (Stefan), Bonnycastle, L. L. (Lori L.), Bork-Jensen, J. (Jette), Brandslund, I. (Ivan), Braund, P. S. (Peter S.), Burgess, S. (Stephen), Cho, K. (Kelly), Christensen, C. (Cramer), Connell, J. (John), de Mutsert, R. (Renee), Dominiczak, A. F. (Anna F.), Dorr, M. (Marcus), Eiriksdottir, G. (Gudny), Farmaki, A.-E. (Aliki-Eleni), Gaziano, J. M. (J. Michael), Grarup, N. (Niels), Grove, M. L. (Megan L.), Hallmans, G. (Goran), Hansen, T. (Torben), Have, C. T. (Christian T.), Heiss, G. (Gerardo), Jorgensen, M. E. (Marit E.), Jousilahti, P. (Pekka), Kajantie, E. (Eero), Kamat, M. (Mihir), Karajamaki, A. (AnneMari), Karpe, F. (Fredrik), Koistinen, H. A. (Heikki A.), Kovesdy, C. P. (Csaba P.), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Lannfelt, L. (Lars), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Linneberg, A. (Allan), Martin, L. W. (Lisa W.), Moitry, M. (Marie), Nadkarni, G. (Girish), Neville, M. J. (Matt J.), Palmer, C. N. (Colin N. A.), Papanicolaou, G. J. (George J.), Pedersen, O. (Oluf), Peters, J. (James), Poulter, N. (Neil), Rasheed, A. (Asif), Rasmussen, K. L. (Katrine L.), Rayner, N. W. (N. William), Magi, R. (Reedik), Renstrom, F. (Frida), Rettig, R. (Rainer), Rossouw, J. (Jacques), Schreiner, P. J. (Pamela J.), Sever, P. S. (Peter S.), Sigurdsson, E. L. (Emil L.), Skaaby, T. (Tea), Sun, Y. V. (Yan, V), Sundstrom, J. (Johan), Thorgeirsson, G. (Gudmundur), Esko, T. (Tonu), Trabetti, E. (Elisabetta), Tsao, P. S. (Philip S.), Tuomi, T. (Tiinamaija), Turner, S. T. (Stephen T.), Tzoulaki, I. (Ioanna), Vaartjes, I. (Ilonca), Vergnaud, A.-C. (Anne-Claire), Willer, C. J. (Cristen J.), Wilson, P. W. (Peter W. F.), Witte, D. R. (Daniel R.), Yonova-Doing, E. (Ekaterina), Zhang, H. (He), Aliya, N. (Naheed), Almgren, P. (Peter), Amouyel, P. (Philippe), Asselbergs, F. W. (Folkert W.), Barnes, M. R. (Michael R.), Blakemore, A. I. (Alexandra, I), Boehnke, M. (Michael), Bots, M. L. (Michiel L.), Bottinger, E. P. (Erwin P.), Buring, J. E. (Julie E.), Chambers, J. C. (John C.), Chen, Y. I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Conen, D. (David), Correa, A. (Adolfo), Smith, G. D. (George Davey), de Boer, R. A. (Rudolf A.), Deary, I. J. (Ian J.), Dedoussis, G. (George), Deloukas, P. (Panos), Di Angelantonio, E. (Emanuele), Elliott, P. (Paul), Felix, S. B. (Stephan B.), Ferrieres, J. (Jean), Ford, I. (Ian), Fornage, M. (Myriam), Franks, P. W. (Paul W.), Franks, S. (Stephen), Frossard, P. (Philippe), Gambaro, G. (Giovanni), Gaunt, T. R. (Tom R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Harris, T. B. (Tamara B.), Hayward, C. (Caroline), Hennig, B. J. (Branwen J.), Herzig, K.-H. (Karl-Heinz), Ingelsson, E. (Erik), Tuomilehto, J. (Jaakko), Järvelin, M.-R. (Marjo-Riitta), Jukema, J. W. (J. Wouter), Kardia, S. L. (Sharon L. R.), Kee, F. (Frank), Kooner, J. S. (Jaspal S.), Kooperberg, C. (Charles), Launer, L. J. (Lenore J.), Lind, L. (Lars), Loos, R. J. (Ruth J. F.), Majumder, A. A. (Abdulla Al Shafi), Laakso, M. (Markku), McCarthy, M. I. (Mark, I), Melander, O. (Olle), Mohlke, K. L. (Karen L.), Murray, A. D. (Alison D.), Nordestgaard, B. G. (Borge Gronne), Orho-Melander, M. (Marju), Packard, C. J. (Chris J.), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Polasek, O. (Ozren), Porteous, D. J. (David J.), Prentice, A. M. (Andrew M.), Province, M. A. (Michael A.), Relton, C. L. (Caroline L.), Rice, K. (Kenneth), Ridker, P. M. (Paul M.), Rolandsson, O. (Olov), Rosendaal, F. R. (Frits R.), Rotter, J. I. (Jerome, I), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N. J. (Nilesh J.), Sattar, N. (Naveed), Sheu, W. H. (Wayne H-H), Smith, B. H. (Blair H.), Soranzo, N. (Nicole), Spector, T. D. (Timothy D.), Starr, J. M. (John M.), Sebert, S. (Sylvain), Taylor, K. D. (Kent D.), Lakka, T. A. (Timo A.), Timpson, N. J. (Nicholas J.), Tobin, M. D. (Martin D.), van der Harst, P. (Pim), van der Meer, P. (Peter), Ramachandran, V. S. (Vasan S.), Verweij, N. (Niek), Virtamo, J. (Jarmo), Volker, U. (Uwe), Weir, D. R. (David R.), Zeggini, E. (Eleftheria), Charchar, F. J. (Fadi J.), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Tomaszewski, M. (Maciej), Butterworth, A. S. (Adam S.), Caulfield, M. J. (Mark J.), Danesh, J. (John), Edwards, T. L. (Todd L.), Holm, H. (Hilma), Hung, A. M. (Adriana M.), Lindgren, C. M. (Cecilia M.), Liu, C. (Chunyu), Manning, A. K. (Alisa K.), Morris, A. P. (Andrew P.), Morrison, A. C. (Alanna C.), O'Donnell, C. J. (Christopher J.), Psaty, B. M. (Bruce M.), Saleheen, D. (Danish), Stefansson, K. (Kari), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel, I), Levy, D. (Daniel), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), Howson, J. M. (Joanna M. M.), Surendran, P. (Praveen), Feofanova, E. V. (Elena, V), Lahrouchi, N. (Najim), Ntalla, I. (Ioanna), Karthikeyan, S. (Savita), Cook, J. (James), Chen, L. (Lingyan), Mifsud, B. (Borbala), Yao, C. (Chen), Kraja, A. T. (Aldi T.), Cartwright, J. H. (James H.), Hellwege, J. N. (Jacklyn N.), Giri, A. (Ayush), Tragante, V. (Vinicius), Thorleifsson, G. (Gudmar), Liu, D. J. (Dajiang J.), Prins, B. P. (Bram P.), Stewart, I. D. (Isobel D.), Cabrera, C. P. (Claudia P.), Eales, J. M. (James M.), Akbarov, A. (Artur), Auer, P. L. (Paul L.), Bielak, L. F. (Lawrence F.), Bis, J. C. (Joshua C.), Braithwaite, V. S. (Vickie S.), Brody, J. A. (Jennifer A.), Daw, E. W. (E. Warwick), Warren, H. R. (Helen R.), Drenos, F. (Fotios), Nielsen, S. F. (Sune Fallgaard), Faul, J. D. (Jessica D.), Fauman, E. B. (Eric B.), Fava, C. (Cristiano), Ferreira, T. (Teresa), Foley, C. N. (Christopher N.), Franceschini, N. (Nora), Gao, H. (He), Giannakopoulou, O. (Olga), Giulianini, F. (Franco), Gudbjartsson, D. F. (Daniel F.), Guo, X. (Xiuqing), Harris, S. E. (Sarah E.), Havulinna, A. S. (Aki S.), Helgadottir, A. (Anna), Huffman, J. E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Kanoni, S. (Stavroula), Kontto, J. (Jukka), Larson, M. G. (Martin G.), Li-Gao, R. (Ruifang), Lindstrom, J. (Jaana), Lotta, L. A. (Luca A.), Lu, Y. (Yingchang), Luan, J. (Jian'an), Mahajan, A. (Anubha), Malerba, G. (Giovanni), Masca, N. G. (Nicholas G. D.), Mei, H. (Hao), Menni, C. (Cristina), Mook-Kanamori, D. O. (Dennis O.), Mosen-Ansorena, D. (David), Muller-Nurasyid, M. (Martina), Pare, G. (Guillaume), Paul, D. S. (Dirk S.), Perola, M. (Markus), Poveda, A. (Alaitz), Rauramaa, R. (Rainer), Richard, M. (Melissa), Richardson, T. G. (Tom G.), Sepulveda, N. (Nuno), Sim, X. (Xueling), Smith, A. V. (Albert, V), Smith, J. A. (Jennifer A.), Staley, J. R. (James R.), Stanakova, A. (Alena), Sulem, P. (Patrick), Theriault, S. (Sebastien), Thorsteinsdottir, U. (Unnur), Trompet, S. (Stella), Varga, T. V. (Tibor V.), Edwards, D. R. (Digna R. Velez), Veronesi, G. (Giovanni), Weiss, S. (Stefan), Willems, S. M. (Sara M.), Yao, J. (Jie), Young, R. (Robin), Yu, B. (Bing), Zhang, W. (Weihua), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Evangelou, E. (Evangelos), Aeschbacher, S. (Stefanie), Asllanaj, E. (Eralda), Blankenberg, S. (Stefan), Bonnycastle, L. L. (Lori L.), Bork-Jensen, J. (Jette), Brandslund, I. (Ivan), Braund, P. S. (Peter S.), Burgess, S. (Stephen), Cho, K. (Kelly), Christensen, C. (Cramer), Connell, J. (John), de Mutsert, R. (Renee), Dominiczak, A. F. (Anna F.), Dorr, M. (Marcus), Eiriksdottir, G. (Gudny), Farmaki, A.-E. (Aliki-Eleni), Gaziano, J. M. (J. Michael), Grarup, N. (Niels), Grove, M. L. (Megan L.), Hallmans, G. (Goran), Hansen, T. (Torben), Have, C. T. (Christian T.), Heiss, G. (Gerardo), Jorgensen, M. E. (Marit E.), Jousilahti, P. (Pekka), Kajantie, E. (Eero), Kamat, M. (Mihir), Karajamaki, A. (AnneMari), Karpe, F. (Fredrik), Koistinen, H. A. (Heikki A.), Kovesdy, C. P. (Csaba P.), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Lannfelt, L. (Lars), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Linneberg, A. (Allan), Martin, L. W. (Lisa W.), Moitry, M. (Marie), Nadkarni, G. (Girish), Neville, M. J. (Matt J.), Palmer, C. N. (Colin N. A.), Papanicolaou, G. J. (George J.), Pedersen, O. (Oluf), Peters, J. (James), Poulter, N. (Neil), Rasheed, A. (Asif), Rasmussen, K. L. (Katrine L.), Rayner, N. W. (N. William), Magi, R. (Reedik), Renstrom, F. (Frida), Rettig, R. (Rainer), Rossouw, J. (Jacques), Schreiner, P. J. (Pamela J.), Sever, P. S. (Peter S.), Sigurdsson, E. L. (Emil L.), Skaaby, T. (Tea), Sun, Y. V. (Yan, V), Sundstrom, J. (Johan), Thorgeirsson, G. (Gudmundur), Esko, T. (Tonu), Trabetti, E. (Elisabetta), Tsao, P. S. (Philip S.), Tuomi, T. (Tiinamaija), Turner, S. T. (Stephen T.), Tzoulaki, I. (Ioanna), Vaartjes, I. (Ilonca), Vergnaud, A.-C. (Anne-Claire), Willer, C. J. (Cristen J.), Wilson, P. W. (Peter W. F.), Witte, D. R. (Daniel R.), Yonova-Doing, E. (Ekaterina), Zhang, H. (He), Aliya, N. (Naheed), Almgren, P. (Peter), Amouyel, P. (Philippe), Asselbergs, F. W. (Folkert W.), Barnes, M. R. (Michael R.), Blakemore, A. I. (Alexandra, I), Boehnke, M. (Michael), Bots, M. L. (Michiel L.), Bottinger, E. P. (Erwin P.), Buring, J. E. (Julie E.), Chambers, J. C. (John C.), Chen, Y. I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Conen, D. (David), Correa, A. (Adolfo), Smith, G. D. (George Davey), de Boer, R. A. (Rudolf A.), Deary, I. J. (Ian J.), Dedoussis, G. (George), Deloukas, P. (Panos), Di Angelantonio, E. (Emanuele), Elliott, P. (Paul), Felix, S. B. (Stephan B.), Ferrieres, J. (Jean), Ford, I. (Ian), Fornage, M. (Myriam), Franks, P. W. (Paul W.), Franks, S. (Stephen), Frossard, P. (Philippe), Gambaro, G. (Giovanni), Gaunt, T. R. (Tom R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Harris, T. B. (Tamara B.), Hayward, C. (Caroline), Hennig, B. J. (Branwen J.), Herzig, K.-H. (Karl-Heinz), Ingelsson, E. (Erik), Tuomilehto, J. (Jaakko), Järvelin, M.-R. (Marjo-Riitta), Jukema, J. W. (J. Wouter), Kardia, S. L. (Sharon L. R.), Kee, F. (Frank), Kooner, J. S. (Jaspal S.), Kooperberg, C. (Charles), Launer, L. J. (Lenore J.), Lind, L. (Lars), Loos, R. J. (Ruth J. F.), Majumder, A. A. (Abdulla Al Shafi), Laakso, M. (Markku), McCarthy, M. I. (Mark, I), Melander, O. (Olle), Mohlke, K. L. (Karen L.), Murray, A. D. (Alison D.), Nordestgaard, B. G. (Borge Gronne), Orho-Melander, M. (Marju), Packard, C. J. (Chris J.), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Polasek, O. (Ozren), Porteous, D. J. (David J.), Prentice, A. M. (Andrew M.), Province, M. A. (Michael A.), Relton, C. L. (Caroline L.), Rice, K. (Kenneth), Ridker, P. M. (Paul M.), Rolandsson, O. (Olov), Rosendaal, F. R. (Frits R.), Rotter, J. I. (Jerome, I), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N. J. (Nilesh J.), Sattar, N. (Naveed), Sheu, W. H. (Wayne H-H), Smith, B. H. (Blair H.), Soranzo, N. (Nicole), Spector, T. D. (Timothy D.), Starr, J. M. (John M.), Sebert, S. (Sylvain), Taylor, K. D. (Kent D.), Lakka, T. A. (Timo A.), Timpson, N. J. (Nicholas J.), Tobin, M. D. (Martin D.), van der Harst, P. (Pim), van der Meer, P. (Peter), Ramachandran, V. S. (Vasan S.), Verweij, N. (Niek), Virtamo, J. (Jarmo), Volker, U. (Uwe), Weir, D. R. (David R.), Zeggini, E. (Eleftheria), Charchar, F. J. (Fadi J.), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Tomaszewski, M. (Maciej), Butterworth, A. S. (Adam S.), Caulfield, M. J. (Mark J.), Danesh, J. (John), Edwards, T. L. (Todd L.), Holm, H. (Hilma), Hung, A. M. (Adriana M.), Lindgren, C. M. (Cecilia M.), Liu, C. (Chunyu), Manning, A. K. (Alisa K.), Morris, A. P. (Andrew P.), Morrison, A. C. (Alanna C.), O'Donnell, C. J. (Christopher J.), Psaty, B. M. (Bruce M.), Saleheen, D. (Danish), Stefansson, K. (Kari), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel, I), Levy, D. (Daniel), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), and Howson, J. M. (Joanna M. M.)
Abstract: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 x 10(⁻⁸)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets., Correction A Publisher Correction to this article was published on 16 March 2021.
Published: 2020

8. Patient‐reported outcomes after 10‐year follow‐up of intensive, multifactorial treatment in individuals with screen‐detected type 2 diabetes:: the ADDITION‐Europe trial

Author: HAG Zorginnovatieonderzoek, Cardiovasculaire Epi Team 5, Dalsgaard, E. M., Sandbæk, A., Griffin, S. J., Rutten, G. E.H.M., Khunti, K., Davies, M. J., Irving, G. J., Vos, R. C., Webb, D. R., Wareham, N. J., Witte, D. R., HAG Zorginnovatieonderzoek, Cardiovasculaire Epi Team 5, Dalsgaard, E. M., Sandbæk, A., Griffin, S. J., Rutten, G. E.H.M., Khunti, K., Davies, M. J., Irving, G. J., Vos, R. C., Webb, D. R., Wareham, N. J., and Witte, D. R.
Published: 2020

9. Prospective association between late evening food consumption and risk of prediabetes and diabetes: the Whitehall II cohort study

Author: Faerch, K., Quist, J. S., Hulman, A., Witte, D. R., Tabak, A. G., Brunner, E. J., Kivimaki, M., Jorgensen, M. E., Panda, S., Vistisen, D., Faerch, K., Quist, J. S., Hulman, A., Witte, D. R., Tabak, A. G., Brunner, E. J., Kivimaki, M., Jorgensen, M. E., Panda, S., and Vistisen, D.
Abstract: Aims We examined whether late evening food consumption was prospectively associated with the risk of developing prediabetes or diabetes in a large observational study of individuals with normoglycaemia. Methods Participants were 2642 men and women with normoglycaemia (HbA(1c) < 39 mmol/mol; < 5.7%) from the Whitehall II study. Time of last eating episode (TLEE) before the examination day was assessed at baseline. We studied the associations of TLEE with 5-year changes in HbA(1c) and risk of developing prediabetes or diabetes (HbA(1c) >= 39 mmol/mol; >= 5.7%). Potential heterogeneity in the association between TLEE and prediabetes or diabetes was examined using recursive partitioning modelling for time-to-event outcomes. Results There was a tendency of an overall association of TLEE with change in HbA(1c) but with little effect size [beta per 1-h increase in TLEE = 0.2 mmol/mol, 95% CI -0.0 to 0.3 (0.01%, -0.00 to 0.03); P = 0.055] and no association with the risk of developing prediabetes/diabetes (risk ratio per 1-h increase in TLEE = 1.03, 95% CI 0.94 to 1.13; P = 0.511). According to the recursive partitioning modelling, women with HbA(1c) <= 36 mmol/mol and TLEE after 21:00 had a 1.51 times (95% CI 1.16 to 1.93) higher 5-year risk of developing prediabetes or diabetes than those having their TLEE between 16:00 and 21:00 (35.4% vs. 23.5%; P = 0.003). Conclusions There was no overall association of TLEE with the development of prediabetes or diabetes in the Whitehall II population. However, explorative analyses suggested that eating late in the evening was associated with increased risk of developing prediabetes/diabetes among women with good glycaemic control. Whether restricting late evening food consumption is effective and feasible for the prevention of Type 2 diabetes needs testing in randomized controlled trials.
Published: 2019

10. Trajectories of obesity by spousal diabetes status in the English Longitudinal Study of Ageing

Author: Silverman-Retana, O, Hulman, A, Simmons, R K, Nielsen, Jannie, Witte, D. R., Silverman-Retana, O, Hulman, A, Simmons, R K, Nielsen, Jannie, and Witte, D. R.
Abstract: AIMS: To examine whether the development of obesity with age was different for individuals with and without a spouse with diabetes.METHODS: We analysed data from the English Longitudinal Study of Ageing [n= 7123, median (interquartile range) age 59 (53-67) years, 51% men], which included four clinical examination waves between 1998 and 2012. The main exposure was having a spouse with diabetes. Outcomes of interest were BMI and waist circumference. We fitted quadratic age-related trajectories using mixed-effect models stratified by sex and adjusted for education, smoking and the corresponding interaction terms between age and spousal diabetes status.RESULTS: The baseline spousal diabetes prevalence was 4.4%. Men with a wife with diabetes experienced a steeper increase in BMI (1.6 kg/m2 ) between ages 50 to 65 years than men with a wife without diabetes (0.9 kg/m2 ). Women with a husband with diabetes had a similarly shaped BMI trajectory to women with a husband without diabetes, but their average BMI levels were higher between ages 55 and 65 years. Waist circumference trajectories showed a similar shape by spousal diabetes status for men and women, although individuals with a spouse with diabetes had higher waist circumference values throughout follow-up.CONCLUSIONS: We found a positive association between spousal diabetes status and obesity development, which differed by sex among middle-aged individuals. Evidence from couple-based interventions is needed to test whether the latter could improve the current individual-focused public health strategies for obesity prevention.
Published: 2019

11. Prospective association between late evening food consumption and risk of prediabetes and diabetes: the Whitehall II cohort study

Author: Faerch, K., Quist, J. S., Hulman, A., Witte, D. R., Tabak, A. G., Brunner, E. J., Kivimaki, M., Jorgensen, M. E., Panda, S., Vistisen, D., Faerch, K., Quist, J. S., Hulman, A., Witte, D. R., Tabak, A. G., Brunner, E. J., Kivimaki, M., Jorgensen, M. E., Panda, S., and Vistisen, D.
Abstract: Aims We examined whether late evening food consumption was prospectively associated with the risk of developing prediabetes or diabetes in a large observational study of individuals with normoglycaemia. Methods Participants were 2642 men and women with normoglycaemia (HbA(1c) < 39 mmol/mol; < 5.7%) from the Whitehall II study. Time of last eating episode (TLEE) before the examination day was assessed at baseline. We studied the associations of TLEE with 5-year changes in HbA(1c) and risk of developing prediabetes or diabetes (HbA(1c) >= 39 mmol/mol; >= 5.7%). Potential heterogeneity in the association between TLEE and prediabetes or diabetes was examined using recursive partitioning modelling for time-to-event outcomes. Results There was a tendency of an overall association of TLEE with change in HbA(1c) but with little effect size [beta per 1-h increase in TLEE = 0.2 mmol/mol, 95% CI -0.0 to 0.3 (0.01%, -0.00 to 0.03); P = 0.055] and no association with the risk of developing prediabetes/diabetes (risk ratio per 1-h increase in TLEE = 1.03, 95% CI 0.94 to 1.13; P = 0.511). According to the recursive partitioning modelling, women with HbA(1c) <= 36 mmol/mol and TLEE after 21:00 had a 1.51 times (95% CI 1.16 to 1.93) higher 5-year risk of developing prediabetes or diabetes than those having their TLEE between 16:00 and 21:00 (35.4% vs. 23.5%; P = 0.003). Conclusions There was no overall association of TLEE with the development of prediabetes or diabetes in the Whitehall II population. However, explorative analyses suggested that eating late in the evening was associated with increased risk of developing prediabetes/diabetes among women with good glycaemic control. Whether restricting late evening food consumption is effective and feasible for the prevention of Type 2 diabetes needs testing in randomized controlled trials.
Published: 2019

12. First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes

Author: Cousminer, DL, Ahlqvist, E, Mishra, R, Andersen, MK, Chesi, A, Hawa, MI, Davis, A, Hodge, KM, Bradfield, JP, Zhou, K, Guy, VC, Akerlund, M, Wod, M, Fritsche, LG, Vestergaard, H, Snyder, J, Hojlund, K, Linneberg, A, Karajamaki, A, Brandslund, I, Kim, CE, Witte, D, Sorgjerd, EP, Brillon, DJ, Pedersen, O, Beck-Nielsen, H, Grarup, N, Pratley, RE, Rickels, MR, Vella, A, Ovalle, F, Melander, O, Harris, RI, Varvel, S, Grill, VER, Hakonarson, H, Froguel, P, Lonsdale, JT, Mauricio, D, Schloot, NC, Khunti, K, Greenbaum, CJ, Asvold, BO, Yderstraede, KB, Pearson, ER, Schwartz, S, Voight, BF, Hansen, T, Tuomi, T, Boehm, BO, Groop, L, Leslie, RD, Grant, SFA, Cousminer, DL, Ahlqvist, E, Mishra, R, Andersen, MK, Chesi, A, Hawa, MI, Davis, A, Hodge, KM, Bradfield, JP, Zhou, K, Guy, VC, Akerlund, M, Wod, M, Fritsche, LG, Vestergaard, H, Snyder, J, Hojlund, K, Linneberg, A, Karajamaki, A, Brandslund, I, Kim, CE, Witte, D, Sorgjerd, EP, Brillon, DJ, Pedersen, O, Beck-Nielsen, H, Grarup, N, Pratley, RE, Rickels, MR, Vella, A, Ovalle, F, Melander, O, Harris, RI, Varvel, S, Grill, VER, Hakonarson, H, Froguel, P, Lonsdale, JT, Mauricio, D, Schloot, NC, Khunti, K, Greenbaum, CJ, Asvold, BO, Yderstraede, KB, Pearson, ER, Schwartz, S, Voight, BF, Hansen, T, Tuomi, T, Boehm, BO, Groop, L, Leslie, RD, and Grant, SFA
Abstract: OBJECTIVE: Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype. RESEARCH DESIGN AND METHODS: We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396). RESULTS: The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes. CONCLUSIONS: Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.
Published: 2018

13. Familial diabetes status and the risk of incident type 2 diabetes in Denmark

Author: Silverman-Retana, O., Hulman, A., Nielsen, J., Ekstrom, C. T., Carstensen, B., Simmons, R. K., Witte, D. R., Silverman-Retana, O., Hulman, A., Nielsen, J., Ekstrom, C. T., Carstensen, B., Simmons, R. K., and Witte, D. R.
Published: 2018

14. Familial diabetes status and the risk of incident type 2 diabetes in Denmark

Author: Silverman-Retana, O., Hulman, A., Nielsen, J., Ekstrom, C. T., Carstensen, B., Simmons, R. K., Witte, D. R., Silverman-Retana, O., Hulman, A., Nielsen, J., Ekstrom, C. T., Carstensen, B., Simmons, R. K., and Witte, D. R.
Published: 2018

15. The non-coding RNA landscape of human hematopoiesis and leukemia

Author: Schwarzer, A. (Adrian), Emmrich, S. (Stephan), Schmidt, F. (Franziska), Beck, D. (Dominik), Ng, M. (Michelle), Reimer, C. (Christina), Adams, F.F. (Felix Ferdinand), Grasedieck, S. (Sarah), Witte, D. (Damian), Käbler, S. (Sebastian), Wong, J.W.H. (Jason W.H.), Shah, A. (Anushi), Huang, Y. (Yizhou), Jammal, R. (Razan), Maroz, A. (Aliaksandra), Jongen-Lavrencic, M. (Mojca), Schambach, A. (Axel), Kuchenbauer, F. (Florian), Pimanda, J.E. (John), Reinhardt, D. (Dirk), Heckl, D. (Dirk), Klusmann, J.-H., Schwarzer, A. (Adrian), Emmrich, S. (Stephan), Schmidt, F. (Franziska), Beck, D. (Dominik), Ng, M. (Michelle), Reimer, C. (Christina), Adams, F.F. (Felix Ferdinand), Grasedieck, S. (Sarah), Witte, D. (Damian), Käbler, S. (Sebastian), Wong, J.W.H. (Jason W.H.), Shah, A. (Anushi), Huang, Y. (Yizhou), Jammal, R. (Razan), Maroz, A. (Aliaksandra), Jongen-Lavrencic, M. (Mojca), Schambach, A. (Axel), Kuchenbauer, F. (Florian), Pimanda, J.E. (John), Reinhardt, D. (Dirk), Heckl, D. (Dirk), and Klusmann, J.-H.
Abstract: Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis. Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells. Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy.
Published: 2017
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16. Convective Concrete: Additive Manufacturing to facilitate activation of thermal mass

Author: de Witte, D. (author), de Klijn-Chevalerias, M.L. (author), Loonen, R.C.G.M. (author), Hensen, J.L.M. (author), Knaack, U. (author), Zimmermann, G. (author), de Witte, D. (author), de Klijn-Chevalerias, M.L. (author), Loonen, R.C.G.M. (author), Hensen, J.L.M. (author), Knaack, U. (author), and Zimmermann, G. (author)
Abstract: This paper reports on the research-driven design process of an innovative thermal mass concept: Convective Concrete. The goal is to improve building energy efficiency and comfort levels by addressing some of the shortcomings of conventional building slabs with high thermal storage capacity. Such heavyweight constructions tend to have a slow response time and do not make effective use of the available thermal mass. Convective Concrete explores new ways of making more intelligent use of thermal mass in buildings. To accomplish this on-demand charging of thermal mass, a network of ducts and fans is embedded in the concrete wall element. This is done by developing customized formwork elements in combination with advanced concrete mixtures. To achieve an efficient airflow rate, the embedded lost formwork and the concrete itself function like a lung. The convection takes place with separate pipes on both sides of the concrete’s core to increase the charge/discharge of the thermal storage process. The first stage of the research, described in this paper, is to simulate the Convective Concrete at the component level, whereupon a mock-up is tested in a climate test set-up. The paper concludes with describing planned activities for turning this concept into a real building product., Design of Constrution
Published: 2017
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17. Assisting the development of innovative responsive façade elements using building performance simulation

Author: de Klijn-Chevalerias, M.L. (author), Loonen, R.C.G.M. (author), Zarzycka, A. (author), de Witte, D. (author), Sarakinioti, M.V. (author), Hensen, J.L.M. (author), de Klijn-Chevalerias, M.L. (author), Loonen, R.C.G.M. (author), Zarzycka, A. (author), de Witte, D. (author), Sarakinioti, M.V. (author), and Hensen, J.L.M. (author)
Abstract: Thermal mass is usually positively associated with energy efficiency and thermal comfort in buildings. However, the slow response of heavyweight constructions is not beneficial at all times, as these dynamic effects may actually also increase heating and cooling energy demand during intermittent operation or can cause unwanted discomfort. This study investigates the potential of energy simulations to support the exploration-driven development of two innovative responsive building elements: “Spong3D” and “Convective Concrete”. Both use fluid flow (Spong3D: water, Convective Concrete: air) inside the construction to reduce building energy demand by exploiting the use of natural energy sinks and sources in the ambient environment, aiming to make more intelligent use of thermal mass. During the development of these concepts, different simulation tools were used alongside experiments for e.g. materials selection, climate analysis, comfort prediction and risk assessment. By presenting the results from a series of simulation studies and by reflecting on their application, this paper shows how computational building performance analyses can play a useful role in ill-defined R&D processes., Design of Constrution, Design Informatics
Published: 2017

18. Assisting the development of innovative responsive façade elements using building performance simulation

Author: de Klijn, M.L., Loonen, R.C.G.M., Zarzycka, Aleksandra, de Witte, D., Sarakinioti, V., Hensen, J.L.M., de Klijn, M.L., Loonen, R.C.G.M., Zarzycka, Aleksandra, de Witte, D., Sarakinioti, V., and Hensen, J.L.M.
Abstract: Thermal mass is usually positively associated with energy efficiency and thermal comfort in buildings. However, the slow response of heavyweight constructions is not beneficial at all times, as these dynamic effects may actually also increase heating and cooling energy demand during intermittent operation or can cause unwanted discomfort. This study investigates the potential of energy simulations to support the exploration-driven development of two innovative responsive building elements: “Spong3D” and “Convective Concrete”. Both use fluid flow (Spong3D: water, Convective Concrete: air) inside the construction to reduce building energy demand by exploiting the use of natural energy sinks and sources in the ambient environment, aiming to make more intelligent use of thermal mass. During the development of these concepts, different simulation tools were used alongside experiments for e.g. materials selection, climate analysis, comfort prediction and risk assessment. By presenting the results from a series of simulation studies and by reflecting on their application, this paper shows how computational building performance analyses can play a useful role in ill-defined R&D processes.
Published: 2017

19. Convective concrete : additive manufacturing to facilitate activation of thermal mass

Author: de Witte, D., de Klijn, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Knaack, U., Zimmermann, G., de Witte, D., de Klijn, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Knaack, U., and Zimmermann, G.
Abstract: This paper reports on the research-driven design process of an innovative thermal mass concept: Convective Concrete. The goal is to improve building energy efficiency and comfort levels by addressing some of the shortcomings of conventional building slabs with high thermal storage capacity. Such heavyweight constructions tend to have a slow response time and do not make effective use of the available thermal mass. Convective Concrete explores new ways of making more intelligent use of thermal mass in buildings. To accomplish this on-demand charging of thermal mass, a network of ducts and fans is embedded in the concrete wall element. This is done by developing customized formwork elements in combination with advanced concrete mixtures. To achieve an efficient airflow rate, the embedded lost formwork and the concrete itself function like a lung. The convection takes place with separate pipes on both sides of the concrete’s core to increase the charge/discharge of the thermal storage process. The first stage of the research, described in this paper, is to simulate the Convective Concrete at the component level, whereupon a mock-up is tested in a climate test set-up. The paper concludes with describing planned activities for turning this concept into a real building product.
Published: 2017

20. Convective Concrete: Additive Manufacturing to facilitate activation of thermal mass

Author: de Witte, D., de Klijn, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Knaack, U., Zimmermann, G., de Witte, D., de Klijn, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Knaack, U., and Zimmermann, G.
Abstract: This paper reports on the research-driven design process of an innovative thermal mass concept: Convective Concrete. The goal is to improve building energy efficiency and comfort levels by addressing some of the shortcomings of conventional building slabs with high thermal storage capacity. Such heavyweight constructions tend to have a slow response time and do not make effective use of the available thermal mass. Convective Concrete explores new ways of making more intelligent use of thermal mass in buildings. To accomplish this on-demand charging of thermal mass, a network of ducts and fans is embedded in the concrete wall element. This is done by developing customized formwork elements in combination with advanced concrete mixtures. To achieve an efficient airflow rate, the embedded lost formwork and the concrete itself function like a lung. The convection takes place with separate pipes on both sides of the concrete’s core to increase the charge/discharge of the thermal storage process. The first stage of the research, described in this paper, is to simulate the Convective Concrete at the component level, whereupon a mock-up is tested in a climate test set-up. The paper concludes with describing planned activities for turning this concept into a real building product.
Published: 2017

21. Convective Concrete: additive manufacturing to facilitate activation of thermal mass

Author: de Witte, D., Knaack, U., de Klijn-Chevalerias, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Zimmermann, G., de Witte, D., Knaack, U., de Klijn-Chevalerias, M.L., Loonen, R.C.G.M., Hensen, J.L.M., and Zimmermann, G.
Abstract: Convective Concrete is about a research-driven design process of an innovative thermal mass concept. The goal is to improve building energy efficiency and comfort levels by addressing some of the shortcomings of conventional building slabs with high thermal storage capacity. Such heavyweight constructions tend to have a slow response time and do not make use of the available thermal mass effectively. Convective Concrete explores new ways of using thermal mass in buildings more intelligently. To accomplish this on-demand charging of thermal mass, a network of ducts and fans is embedded in the concrete wall element. This is done by developing customized formwork elements in combination with advanced concrete mixtures. To achieve an efficient airflow rate, the embedded lost formwork and the concrete itself function like a lung.
Published: 2017

22. Max Weber’s interpretations of medieval canon law and its contemporary narratives of legal history

Author: Gephart, Werner, Witte, Daniel, Gephart, W ( Werner ), Witte, D ( Daniel ), Thier, Andreas, Gephart, Werner, Witte, Daniel, Gephart, W ( Werner ), Witte, D ( Daniel ), and Thier, Andreas
Published: 2017

23. Convective Concrete: additive manufacturing to facilitate activation of thermal mass

Author: de Witte, D., Knaack, U., de Klijn-Chevalerias, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Zimmermann, G., de Witte, D., Knaack, U., de Klijn-Chevalerias, M.L., Loonen, R.C.G.M., Hensen, J.L.M., and Zimmermann, G.
Abstract: Convective Concrete is about a research-driven design process of an innovative thermal mass concept. The goal is to improve building energy efficiency and comfort levels by addressing some of the shortcomings of conventional building slabs with high thermal storage capacity. Such heavyweight constructions tend to have a slow response time and do not make use of the available thermal mass effectively. Convective Concrete explores new ways of using thermal mass in buildings more intelligently. To accomplish this on-demand charging of thermal mass, a network of ducts and fans is embedded in the concrete wall element. This is done by developing customized formwork elements in combination with advanced concrete mixtures. To achieve an efficient airflow rate, the embedded lost formwork and the concrete itself function like a lung.
Published: 2017

24. Assisting the development of innovative responsive façade elements using building performance simulation

Author: de Klijn, M.L., Loonen, R.C.G.M., Zarzycka, Aleksandra, de Witte, D., Sarakinioti, V., Hensen, J.L.M., de Klijn, M.L., Loonen, R.C.G.M., Zarzycka, Aleksandra, de Witte, D., Sarakinioti, V., and Hensen, J.L.M.
Abstract: Thermal mass is usually positively associated with energy efficiency and thermal comfort in buildings. However, the slow response of heavyweight constructions is not beneficial at all times, as these dynamic effects may actually also increase heating and cooling energy demand during intermittent operation or can cause unwanted discomfort. This study investigates the potential of energy simulations to support the exploration-driven development of two innovative responsive building elements: “Spong3D” and “Convective Concrete”. Both use fluid flow (Spong3D: water, Convective Concrete: air) inside the construction to reduce building energy demand by exploiting the use of natural energy sinks and sources in the ambient environment, aiming to make more intelligent use of thermal mass. During the development of these concepts, different simulation tools were used alongside experiments for e.g. materials selection, climate analysis, comfort prediction and risk assessment. By presenting the results from a series of simulation studies and by reflecting on their application, this paper shows how computational building performance analyses can play a useful role in ill-defined R&D processes.
Published: 2017

25. Convective Concrete: Additive Manufacturing to facilitate activation of thermal mass

Author: de Witte, D., de Klijn, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Knaack, U., Zimmermann, G., de Witte, D., de Klijn, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Knaack, U., and Zimmermann, G.
Abstract: This paper reports on the research-driven design process of an innovative thermal mass concept: Convective Concrete. The goal is to improve building energy efficiency and comfort levels by addressing some of the shortcomings of conventional building slabs with high thermal storage capacity. Such heavyweight constructions tend to have a slow response time and do not make effective use of the available thermal mass. Convective Concrete explores new ways of making more intelligent use of thermal mass in buildings. To accomplish this on-demand charging of thermal mass, a network of ducts and fans is embedded in the concrete wall element. This is done by developing customized formwork elements in combination with advanced concrete mixtures. To achieve an efficient airflow rate, the embedded lost formwork and the concrete itself function like a lung. The convection takes place with separate pipes on both sides of the concrete’s core to increase the charge/discharge of the thermal storage process. The first stage of the research, described in this paper, is to simulate the Convective Concrete at the component level, whereupon a mock-up is tested in a climate test set-up. The paper concludes with describing planned activities for turning this concept into a real building product.
Published: 2017

26. Convective concrete : additive manufacturing to facilitate activation of thermal mass

Author: de Witte, D., de Klijn, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Knaack, U., Zimmermann, G., de Witte, D., de Klijn, M.L., Loonen, R.C.G.M., Hensen, J.L.M., Knaack, U., and Zimmermann, G.
Abstract: This paper reports on the research-driven design process of an innovative thermal mass concept: Convective Concrete. The goal is to improve building energy efficiency and comfort levels by addressing some of the shortcomings of conventional building slabs with high thermal storage capacity. Such heavyweight constructions tend to have a slow response time and do not make effective use of the available thermal mass. Convective Concrete explores new ways of making more intelligent use of thermal mass in buildings. To accomplish this on-demand charging of thermal mass, a network of ducts and fans is embedded in the concrete wall element. This is done by developing customized formwork elements in combination with advanced concrete mixtures. To achieve an efficient airflow rate, the embedded lost formwork and the concrete itself function like a lung. The convection takes place with separate pipes on both sides of the concrete’s core to increase the charge/discharge of the thermal storage process. The first stage of the research, described in this paper, is to simulate the Convective Concrete at the component level, whereupon a mock-up is tested in a climate test set-up. The paper concludes with describing planned activities for turning this concept into a real building product.
Published: 2017

27. Assisting the development of innovative responsive façade elements using building performance simulation

Author: de Klijn-Chevalerias, M.L. (author), Loonen, R.C.G.M. (author), Zarzycka, A. (author), de Witte, D. (author), Sarakinioti, M.V. (author), Hensen, J.L.M. (author), de Klijn-Chevalerias, M.L. (author), Loonen, R.C.G.M. (author), Zarzycka, A. (author), de Witte, D. (author), Sarakinioti, M.V. (author), and Hensen, J.L.M. (author)
Abstract: Thermal mass is usually positively associated with energy efficiency and thermal comfort in buildings. However, the slow response of heavyweight constructions is not beneficial at all times, as these dynamic effects may actually also increase heating and cooling energy demand during intermittent operation or can cause unwanted discomfort. This study investigates the potential of energy simulations to support the exploration-driven development of two innovative responsive building elements: “Spong3D” and “Convective Concrete”. Both use fluid flow (Spong3D: water, Convective Concrete: air) inside the construction to reduce building energy demand by exploiting the use of natural energy sinks and sources in the ambient environment, aiming to make more intelligent use of thermal mass. During the development of these concepts, different simulation tools were used alongside experiments for e.g. materials selection, climate analysis, comfort prediction and risk assessment. By presenting the results from a series of simulation studies and by reflecting on their application, this paper shows how computational building performance analyses can play a useful role in ill-defined R&D processes., Design of Constrution, Design Informatics
Published: 2017

28. Convective Concrete: Additive Manufacturing to facilitate activation of thermal mass

Author: de Witte, D. (author), de Klijn-Chevalerias, M.L. (author), Loonen, R.C.G.M. (author), Hensen, J.L.M. (author), Knaack, U. (author), Zimmermann, G. (author), de Witte, D. (author), de Klijn-Chevalerias, M.L. (author), Loonen, R.C.G.M. (author), Hensen, J.L.M. (author), Knaack, U. (author), and Zimmermann, G. (author)
Abstract: This paper reports on the research-driven design process of an innovative thermal mass concept: Convective Concrete. The goal is to improve building energy efficiency and comfort levels by addressing some of the shortcomings of conventional building slabs with high thermal storage capacity. Such heavyweight constructions tend to have a slow response time and do not make effective use of the available thermal mass. Convective Concrete explores new ways of making more intelligent use of thermal mass in buildings. To accomplish this on-demand charging of thermal mass, a network of ducts and fans is embedded in the concrete wall element. This is done by developing customized formwork elements in combination with advanced concrete mixtures. To achieve an efficient airflow rate, the embedded lost formwork and the concrete itself function like a lung. The convection takes place with separate pipes on both sides of the concrete’s core to increase the charge/discharge of the thermal storage process. The first stage of the research, described in this paper, is to simulate the Convective Concrete at the component level, whereupon a mock-up is tested in a climate test set-up. The paper concludes with describing planned activities for turning this concept into a real building product., Design of Constrution
Published: 2017
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29. Trajectories of obesity by spousal diabetes status in the English Longitudinal Study of Ageing

Author: Silverman-Retana, O., Hulman, A., Simmons, R. K., Nielsen, J., Witte, D. R., Silverman-Retana, O., Hulman, A., Simmons, R. K., Nielsen, J., and Witte, D. R.
Published: 2017

30. Spousal diabetes and obesity as risk factors of incident type 2 diabetes:analysis from the English Longitudinal Study of Ageing

Author: Hulman, A., Nielsen, J., Witte, D. R., Hulman, A., Nielsen, J., and Witte, D. R.
Published: 2017

31. The non-coding RNA landscape of human hematopoiesis and leukemia

Author: Schwarzer, A, Emmrich, S, Schmidt, F, Beck, D, Ng, M, Reimer, C, Adams, FF, Grasedieck, S, Witte, D, Käbler, S, Wong, JWH, Shah, A, Huang, Y, Jammal, R, Maroz, A, Jongen-Lavrencic, M, Schambach, A, Kuchenbauer, F, Pimanda, JE, Reinhardt, D, Heckl, D, Klusmann, JH, Schwarzer, A, Emmrich, S, Schmidt, F, Beck, D, Ng, M, Reimer, C, Adams, FF, Grasedieck, S, Witte, D, Käbler, S, Wong, JWH, Shah, A, Huang, Y, Jammal, R, Maroz, A, Jongen-Lavrencic, M, Schambach, A, Kuchenbauer, F, Pimanda, JE, Reinhardt, D, Heckl, D, and Klusmann, JH
Abstract: © The Author(s) 2017. Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis. Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells. Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy.
Published: 2017

32. The non-coding RNA landscape of human hematopoiesis and leukemia

Author: Schwarzer, A, Emmrich, S, Schmidt, F, Beck, D, Ng, M, Reimer, C, Adams, FF, Grasedieck, S, Witte, D, Käbler, S, Wong, JWH, Shah, A, Huang, Y, Jammal, R, Maroz, A, Jongen-Lavrencic, M, Schambach, A, Kuchenbauer, F, Pimanda, JE, Reinhardt, D, Heckl, D, Klusmann, JH, Schwarzer, A, Emmrich, S, Schmidt, F, Beck, D, Ng, M, Reimer, C, Adams, FF, Grasedieck, S, Witte, D, Käbler, S, Wong, JWH, Shah, A, Huang, Y, Jammal, R, Maroz, A, Jongen-Lavrencic, M, Schambach, A, Kuchenbauer, F, Pimanda, JE, Reinhardt, D, Heckl, D, and Klusmann, JH
Abstract: © The Author(s) 2017. Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis. Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells. Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy.
Published: 2017

33. Imagine 10: RAPIDS 2.0

Author: Knaack, U. (author), de Witte, D. (author), Mohsen, Alamir (author), Tessmann, Oliver (author), Bilow, M. (author), Knaack, U. (author), de Witte, D. (author), Mohsen, Alamir (author), Tessmann, Oliver (author), and Bilow, M. (author)
Abstract: In 2014, a 3D-printed Canal House by DUS architects caught the attention of the world – including President Obama. The 3D Print Canal House proved the potentials of Additive Manufacturing for architecture and construction. Additive Manufacturing provides the architect with completely new solutions for realising tool-less production methods while allowing maximum freedom of design. Additive Manufacturing is ideally suited for Rapid Prototyping. It is possible to manufacture physical presentation and functional prototypes with complex shapes quickly and cost-efficiently without the need for manual processing – directly using three-dimensional CAD construction data. This makes the entire product development process considerably faster. Imagine 10 explores the potentials of Additive Manufacturing for architecture by charting the current state of technology, discussing its implications for design and construction processes, and presents research projects as well as concept ideas for future Additive Manufacturing applications., Architectural Engineering +Technology, Building Product Innovation, Design of Constrution
Published: 2016

34. Imagine 10: RAPIDS 2.0

Author: Knaack, U. (author), de Witte, D. (author), Mohsen, Alamir (author), Tessmann, Oliver (author), Bilow, M. (author), Knaack, U. (author), de Witte, D. (author), Mohsen, Alamir (author), Tessmann, Oliver (author), and Bilow, M. (author)
Abstract: In 2014, a 3D-printed Canal House by DUS architects caught the attention of the world – including President Obama. The 3D Print Canal House proved the potentials of Additive Manufacturing for architecture and construction. Additive Manufacturing provides the architect with completely new solutions for realising tool-less production methods while allowing maximum freedom of design. Additive Manufacturing is ideally suited for Rapid Prototyping. It is possible to manufacture physical presentation and functional prototypes with complex shapes quickly and cost-efficiently without the need for manual processing – directly using three-dimensional CAD construction data. This makes the entire product development process considerably faster. Imagine 10 explores the potentials of Additive Manufacturing for architecture by charting the current state of technology, discussing its implications for design and construction processes, and presents research projects as well as concept ideas for future Additive Manufacturing applications., Architectural Engineering +Technology, Building Product Innovation, Design of Constrution
Published: 2016

35. Methylglyoxal is associated with changes in kidney function among individuals with screen-detected Type 2 diabetes mellitus

Author: Jensen, T. M., Vistisen, D., Fleming, T., Nawroth, P. P., Rossing, P., Jørgensen, M. E., Lauritzen, T., Sandbæk, A., Witte, D. R., Jensen, T. M., Vistisen, D., Fleming, T., Nawroth, P. P., Rossing, P., Jørgensen, M. E., Lauritzen, T., Sandbæk, A., and Witte, D. R.
Abstract: Aims: The glycolysis-derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part of the Danish arm of the ADDITION-Europe trial (ADDITION-DK). Methods: Biobank serum samples collected at ADDITION-DK baseline (2001–2006) and follow-up (2009–2010) were used in the current analysis of methylglyoxal. We assessed cross-sectional baseline and longitudinal associations between methylglyoxal and urinary albumin-to-creatinine ratio (ACR) or estimated GFR (eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR. Results: Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow-up was inversely associated with change in eGFR (–1.6 ml/min/1.73 m2 per doubling in methylglyoxal change), in models adjusted for age, sex, HbA1c, systolic blood pressure, anti-hypertensive treatment, LDL-cholesterol, lipid-lowering treatment, C-reactive protein and smoking. Conclusions: In a population of people with screen-detected Type 2 diabetes, we observed associations between methylglyoxal and markers of renal function: 6-year change in methylglyoxal was inversely associated with 6-year change in eGFR. Also, methylglyoxal at baseline was positively associated with ACR at baseline. Our study lends further support to a role for methylglyoxal in the pathogenesis of diabetic nephropathy.
Published: 2016

36. Concrete in an AM process: Freeform concrete processing

Author: De Witte, D. (author) and De Witte, D. (author)
Abstract: This thesis examines the additive manufacturing (AM) of concrete, its possibilities, feasibility and advantages over existing techniques. The first part generally focuses on the characteristic properties of concrete that are important and how they relate to an AM method, for instance aggregates and reinforcement. After this extensive introduction in the field of concrete and AM, the current situation regarding additive manufacturing of concrete is described. On the basis of literature resulting products are shown and discussed. Their characteristics are compared to detect a match or mismatch between the AM technique and the produced elements. The outcome of this evaluation is used to describe improvements which are elaborated in the second part. This design part consists of a roadmap that shows a future vision. Concrete is a new material in the field of additive manufacturing. Since it is one of the materials that hardens by a chemical reaction, considerable attention needs to be paid to the workability of it in an AM process. Traditional processing techniques are adapted to these characteristics but concrete does not let itself dictate how to behave. The roadmap envisions how the technique has to evolve in order to implement the characteristic properties of concrete. The possibilities for products made with an additive process are endless, but just replacing existing production methods with additive ones is impossible. Although improved freeform production techniques are still the aim of this research, this does not mean that more freedom in form is by definition the largest improvement that AM can offer at the moment. From another point of view the implementation of additional functions in traditional products can be of great value. Product ideas and an evaluation of the techniques shown in the vision are related to the developments to achieve an increase in speed, surface quality and strength in the AM production technique, next to the requirements that have to b, Building Technology, Architecture and The Built Environment
Published: 2015

37. Concrete in an AM process: Freeform concrete processing

Author: De Witte, D. (author) and De Witte, D. (author)
Abstract: This thesis examines the additive manufacturing (AM) of concrete, its possibilities, feasibility and advantages over existing techniques. The first part generally focuses on the characteristic properties of concrete that are important and how they relate to an AM method, for instance aggregates and reinforcement. After this extensive introduction in the field of concrete and AM, the current situation regarding additive manufacturing of concrete is described. On the basis of literature resulting products are shown and discussed. Their characteristics are compared to detect a match or mismatch between the AM technique and the produced elements. The outcome of this evaluation is used to describe improvements which are elaborated in the second part. This design part consists of a roadmap that shows a future vision. Concrete is a new material in the field of additive manufacturing. Since it is one of the materials that hardens by a chemical reaction, considerable attention needs to be paid to the workability of it in an AM process. Traditional processing techniques are adapted to these characteristics but concrete does not let itself dictate how to behave. The roadmap envisions how the technique has to evolve in order to implement the characteristic properties of concrete. The possibilities for products made with an additive process are endless, but just replacing existing production methods with additive ones is impossible. Although improved freeform production techniques are still the aim of this research, this does not mean that more freedom in form is by definition the largest improvement that AM can offer at the moment. From another point of view the implementation of additional functions in traditional products can be of great value. Product ideas and an evaluation of the techniques shown in the vision are related to the developments to achieve an increase in speed, surface quality and strength in the AM production technique, next to the requirements that have to b, Building Technology, Architecture and The Built Environment
Published: 2015

38. The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy:the ADDITION Denmark study

Author: Hansen, C. S., Jensen, T.M., Jensen, J S, Nawroth, P, Fleming, T, Witte, D R, Lauritzen, T, Sandbaek, A, Charles, M, Fleischer, J., Vistisen, D., Jørgensen, M. E., Hansen, C. S., Jensen, T.M., Jensen, J S, Nawroth, P, Fleming, T, Witte, D R, Lauritzen, T, Sandbaek, A, Charles, M, Fleischer, J., Vistisen, D., and Jørgensen, M. E.
Abstract: AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration ~ 5.8 years).METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy was assessed by vibration detection threshold (n = 319), 10 g monofilament (n = 543) and the Michigan Neuropathy Screening Instrument questionnaire (n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form (n = 882).RESULTS: No associations between methylglyoxal and cardiovascular autonomic reflex tests or any measures of diabetic peripheral neuropathy or painful diabetic neuropathy were observed. However, a positive association between methylglyoxal and several heart rate variability indices was observed, although these associations were not statistically significant when corrected for multiple testing.CONCLUSION: Serum methylglyoxal is not associated with cardiovascular autonomic neuropathy, diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of well-treated patients with short-term diabetes.
Published: 2015

39. Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility

Author: Guigas, B, de Leeuw van Weenen, J E, van Leeuwen, N, Simonis-Bik, A M, van Haeften, T W, Nijpels, G, Houwing-Duistermaat, J J, Beekman, M, Deelen, J, Havekes, L M, Penninx, B W J H, Vogelzangs, N, van 't Riet, E, Dehghan, A, Hofman, A, Witteman, J C, Uitterlinden, A G, Grarup, Niels, Jørgensen, Torben, Witte, D R, Lauritzen, T, Hansen, Torben, Pedersen, O, Hottenga, J, Romijn, J A, Diamant, M, Kramer, M H H, Heine, R J, Willemsen, G, Dekker, J M, Eekhoff, E M, Pijl, H, de Geus, E J, Slagboom, P E, 't Hart, L M, Guigas, B, de Leeuw van Weenen, J E, van Leeuwen, N, Simonis-Bik, A M, van Haeften, T W, Nijpels, G, Houwing-Duistermaat, J J, Beekman, M, Deelen, J, Havekes, L M, Penninx, B W J H, Vogelzangs, N, van 't Riet, E, Dehghan, A, Hofman, A, Witteman, J C, Uitterlinden, A G, Grarup, Niels, Jørgensen, Torben, Witte, D R, Lauritzen, T, Hansen, Torben, Pedersen, O, Hottenga, J, Romijn, J A, Diamant, M, Kramer, M H H, Heine, R J, Willemsen, G, Dekker, J M, Eekhoff, E M, Pijl, H, de Geus, E J, Slagboom, P E, and 't Hart, L M
Abstract: AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans.METHODS: Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis.RESULTS: rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*10(-4) ) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*10(-4) ) but again not in men (P = 0.34).CONCLUSION: The present data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene.
Published: 2014

40. Quality control and conduct of genome-wide association meta-analyses

Author: Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis, G, Absher, D, Alavere, H, Albrecht, E, Allen, H, Almgren, P, Amin, N, Amouyel, P, Anderson, D, Arnold, A, Arveiler, D, Aspelund, T, Asselbergs, F, Assimes, T, Atalay, M, Attwood, A, Atwood, L, Bakker, S, Balkau, B, Balmforth, A, Barlassina, C, Barroso, I, Basart, H, Bauer, S, Beckmann, J, Beilby, J, Bennett, A, Ben Shlomo, Y, Bergman, R, Bergmann, S, Berndt, S, Biffar, R, Di Blasio, A, Boehm, B, Boehnke, M, Boeing, H, Boerwinkle, E, Bolton, J, Bonnefond, A, Bonnycastle, L, Boomsma, D, Borecki, I, Bornstein, S, Bouatia Naji, N, Boucher, G, Bragg Gresham, J, Brambilla, P, Bruinenberg, M, Buchanan, T, Buechler, C, Cadby, G, Campbell, H, Caulfield, M, Cavalcanti Proença, C, Cesana, G, Chanock, S, Chasman, D, Chen, Y, Chines, P, Clegg, D, Coin, L, Collins, F, Connell, J, Cookson, W, Cooper, M, Cupples, L, Cusi, D, Day, I, Dedoussis, G, Dei, M, Deloukas, P, Dermitzakis, E, Dimas, A, Dimitriou, M, Dixon, A, Dörr, M, van Duijn, C, Ebrahim, S, Edkins, S, Eiriksdottir, G, Eisinger, K, Eklund, N, Elliott, P, Erbel, R, Erdmann, J, Erdos, M, Eriksson, J, Estrada, K, Evans, D, de Faire, U, Farrall, M, Feitosa, M, Ferrario, M, Ferrières, J, Fischer, K, Fisher, E, Fowkes, G, Fox, C, Franke, L, Franks, P, Fraser, R, Frau, F, Frayling, T, Freimer, N, Froguel, P, Fu, M, Gaget, S, Ganna, A, Gejman, P, Gentilini, D, Geus, E, Gieger, C, Gigante, B, Gjesing, A, Glazer, N, Goddard, M, Goel, A, Grallert, H, Gräßler, J, Grönberg, H, Groop, L, Groves, C, Gudnason, V, Guiducci, C, Gyllensten, U, Hall, A, Hall, P, Hallmans, G, Hamsten, A, Hansen, T, Haritunians, T, Harris, T, van der Harst, P, Hartikainen, A, Hassanali, N, Hattersley, A, Havulinna, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, den Heijer, M, Hengstenberg, C, Herzig, K, Hicks, A, Hingorani, A, Hinney, A, Hirschhorn, J, Hofman, A, Holmes, C, Homuth, G, Hottenga, J, Hovingh, K, Hu, F, Hu, Y, Huffman, J, Hui, J, Huikuri, H, Humphries, S, Hung, J, Hunt, S, Hunter, D, Hveem, K, Hyppönen, E, Igl, W, Illig, T, Ingelsson, E, Iribarren, C, Isomaa, B, Jackson, A, Jacobs, K, James, A, Jansson, J, Jarick, I, Jarvelin, M, Jöckel, K, Johansson, Å, Johnson, T, Jolley, J, Jørgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kähönen, M, Kajantie, E, Kanoni, S, Kao, W, Kaplan, L, Kaplan, R, Kaprio, J, Kapur, K, Karpe, F, Kathiresan, S, Kee, F, Keinanen Kiukaanniemi, S, Ketkar, S, Kettunen, J, Khaw, K, Kiemeney, L, Kinnunen, L, Kivimaki, M, Kivmaki, M, Van der Klauw, M, Kleber, M, Knowles, J, Koenig, W, Kolcic, I, Kolovou, G, König, I, Koskinen, S, Kovacs, P, Kraft, P, Kraja, A, Kristiansson, K, Krjutåjkov, K, Kroemer, H, Krohn, J, Krzelj, V, Kuh, D, Kulzer, J, Kumari, M, Kuulasmaa, K, Kuusisto, J, Kvaloy, K, Laakso, M, Laitinen, J, Lakka, T, Lamina, C, Langenberg, C, Lantieri, O, Lathrop, G, Launer, L, Lawlor, D, Lawrence, R, Leach, I, Lecoeur, C, Lee, S, Lehtimäki, T, Leitzmann, M, Lettre, G, Levinson, D, Li, G, Li, S, Liang, L, Lin, D, Lind, L, Lindgren, C, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Loley, C, Lorentzon, M, Luben, R, Ludwig, B, Madden, P, Magnusson, P, Mangino, M, Manunta, P, Marek, D, Marre, M, Martin, N, März, W, Maschio, A, Mathieson, I, Mcardle, W, Mccaroll, S, Mccarthy, A, Mccarthy, M, Mcknight, B, Medina Gomez, C, Medland, S, Meitinger, T, Metspalu, A, van Meurs, J, Meyre, D, Midthjell, K, Mihailov, E, Milani, L, Min, J, Moebus, S, Moffatt, M, Mohlke, K, Molony, C, Monda, K, Montgomery, G, Mooser, V, Morken, M, Morris, A, Mühleisen, T, Müller Nurasyid, M, Munroe, P, Musk, A, Narisu, N, Navis, G, Neale, B, Nelis, M, Nemesh, J, Neville, M, Ngwa, J, Nicholson, G, Nieminen, M, Njølstad, I, Nohr, E, Nolte, I, North, K, Nöthen, M, Nyholt, D, O'Connell, J, Ohlsson, C, Oldehinkel, A, van Ommen, G, Ong, K, Oostra, B, Ouwehand, W, Palmer, C, Palmer, L, Palotie, A, Paré, G, Parker, A, Paternoster, L, Pawitan, Y, Pechlivanis, S, Peden, J, Pedersen, N, Pedersen, O, Pellikka, N, Peltonen, L, Penninx, B, Perola, M, Perry, J, Person, T, Peters, A, Peters, M, Pichler, I, Pietiläinen, K, Platou, C, Polasek, O, Pouta, A, Power, C, Pramstaller, P, Preuss, M, Price, J, Prokopenko, I, Province, M, Psaty, B, Purcell, S, Pütter, C, Qi, L, Quertermous, T, Radhakrishnan, A, Raitakari, O, Rauramaa, R, Rayner, N, Rehnberg, E, Rendon, A, Ridderstråle, M, Ridker, P, Ripatti, S, Rissanen, A, Rivadeneira, F, Rivolta, C, Robertson, N, Rose, L, Rudan, I, Saaristo, T, Sager, H, Salomaa, V, Samani, N, Sambrook, J, Sanders, A, Sandholt, C, Sanna, S, Saramies, J, Schadt, E, Schipf, S, Schlessinger, D, Schreiber, S, Schunkert, H, Schwarz, P, Scott, L, Shi, J, Shin, S, Shuldiner, A, Shungin, D, Signorini, S, Silander, K, Sinisalo, J, Skrobek, B, Smit, J, Smith, A, Smith, G, Snieder, H, Soranzo, N, Sørensen, T, Sovio, U, Spector, T, Speliotes, E, Stančáková, A, Stark, K, Stefansson, K, Steinthorsdottir, V, Stephens, J, Stirrups, K, Stolk, R, Strachan, D, Strawbridge, R, Stringham, H, Stumvoll, M, Surakka, I, Swift, A, Syvanen, A, Tammesoo, M, Teder Laving, M, Teslovich, T, Teumer, A, Theodoraki, E, Thomson, B, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Timpson, N, Tönjes, A, Tregouet, D, Tremoli, E, Trip, M, Tuomi, T, Tuomilehto, J, Tyrer, J, Uda, M, Uitterlinden, A, Usala, G, Uusitupa, M, Valle, T, Vandenput, L, Vatin, V, de Vegt, F, Vermeulen, S, Viikari, J, Virtamo, J, Visscher, P, Vitart, V, Van Vliet Ostaptchouk, J, Voight, B, Vollenweider, P, Volpato, C, Völzke, H, Waeber, G, Waite, L, Wallaschofski, H, Walters, G, Wang, Z, Wareham, N, Watanabe, R, Watkins, H, Weedon, M, Welch, R, Weyant, R, Wheeler, E, White, C, Wichmann, H, Widen, E, Wild, S, Willemsen, G, Willer, C, Wilsgaard, T, Wilson, J, van Wingerden, S, Winkelmann, B, Witte, D, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Yang, J, Yarnell, J, Zgaga, L, Zhao, J, Zillikens, M, Zitting, P, Zondervan, K, Abecasis GR, Absher D, Alavere H, Albrecht E, Allen HL, Almgren P, Amin N, Amouyel P, Anderson D, Arnold AM, Arveiler D, Aspelund T, Asselbergs FW, Assimes TL, Atalay M, Attwood AP, Atwood LD, Bakker SJ, Balkau B, Balmforth AJ, Barlassina C, Barroso I, Basart H, Bauer S, Beckmann JS, Beilby JP, Bennett AJ, Ben Shlomo Y, Bergman RN, Bergmann S, Berndt SI, Biffar R, Di Blasio AM, Boehm BO, Boehnke M, Boeing H, Boerwinkle E, Bolton JL, Bonnefond A, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bouatia Naji N, Boucher G, Bragg Gresham JL, BRAMBILLA, PAOLO, Bruinenberg M, Buchanan TA, Buechler C, Cadby G, Campbell H, Caulfield MJ, Cavalcanti Proença C, CESANA, GIANCARLO, Chanock SJ, Chasman DI, Chen YD, Chines PS, Clegg DJ, Coin L, Collins FS, Connell JM, Cookson W, Cooper MN, Croteau Chonka DC, Cupples LA, Cusi D, Day FR, Day IN, Dedoussis GV, Dei M, Deloukas P, Dermitzakis ET, Dimas AS, Dimitriou M, Dixon AL, Dörr M, van Duijn CM, Ebrahim S, Edkins S, Eiriksdottir G, Eisinger K, Eklund N, Elliott P, Erbel R, Erdmann J, Erdos MR, Eriksson JG, Esko T, Estrada K, Evans DM, de Faire U, Fall T, Farrall M, Feitosa MF, Ferrario MM, Ferreira T, Ferrières J, Fischer K, Fisher E, Fowkes G, Fox CS, Franke L, Franks PW, Fraser RM, Frau F, Frayling T, Freimer NB, Froguel P, Fu M, Gaget S, Ganna A, Gejman PV, Gentilini D, Geus EJ, Gieger C, Gigante B, Gjesing AP, Glazer NL, Goddard ME, Goel A, Grallert H, Gräßler J, Grönberg H, Groop LC, Groves CJ, Gudnason V, Guiducci C, Gustafsson S, Gyllensten U, Hall AS, Hall P, Hallmans G, Hamsten A, Hansen T, Haritunians T, Harris TB, van der Harst P, Hartikainen AL, Hassanali N, Hattersley AT, Havulinna AS, Hayward C, Heard Costa NL, Heath AC, Hebebrand J, Heid IM, den Heijer M, Hengstenberg C, Herzig KH, Hicks AA, Hingorani A, Hinney A, Hirschhorn JN, Hofman A, Holmes CC, Homuth G, Hottenga JJ, Hovingh KG, Hu FB, Hu YJ, Huffman JE, Hui J, Huikuri H, Humphries SE, Hung J, Hunt SE, Hunter D, Hveem K, Hyppönen E, Igl W, Illig T, Ingelsson E, Iribarren C, Isomaa B, Jackson AU, Jacobs KB, James AL, Jansson JO, Jarick I, Jarvelin MR, Jöckel KH, Johansson Å, Johnson T, Jolley J, Jørgensen T, Jousilahti P, Jula A, Justice AE, Kaakinen M, Kähönen M, Kajantie E, Kanoni S, Kao WH, Kaplan LM, Kaplan RC, Kaprio J, Kapur K, Karpe F, Kathiresan S, Kee F, Keinanen Kiukaanniemi SM, Ketkar S, Kettunen J, Khaw KT, Kiemeney LA, Kilpeläinen TO, Kinnunen L, Kivimaki M, Kivmaki M, Van der Klauw MM, Kleber ME, Knowles JW, Koenig W, Kolcic I, Kolovou G, König IR, Koskinen S, Kovacs P, Kraft P, Kraja AT, Kristiansson K, KrjutÅjkov K, Kroemer HK, Krohn JP, Krzelj V, Kuh D, Kulzer JR, Kumari M, Kutalik Z, Kuulasmaa K, Kuusisto J, Kvaloy K, Laakso M, Laitinen JH, Lakka TA, Lamina C, Langenberg C, Lantieri O, Lathrop GM, Launer LJ, Lawlor DA, Lawrence RW, Leach IM, Lecoeur C, Lee SH, Lehtimäki T, Leitzmann MF, Lettre G, Levinson DF, Li G, Li S, Liang L, Lin DY, Lind L, Lindgren CM, Lindström J, Liu J, Liuzzi A, Locke AE, Lokki ML, Loley C, Loos RJ, Lorentzon M, Luan J, Luben RN, Ludwig B, Madden PA, Mägi R, Magnusson PK, Mangino M, Manunta P, Marek D, Marre M, Martin NG, März W, Maschio A, Mathieson I, McArdle WL, McCaroll SA, McCarthy A, McCarthy MI, McKnight B, Medina Gomez C, Medland SE, Meitinger T, Metspalu A, van Meurs JB, Meyre D, Midthjell K, Mihailov E, Milani L, Min JL, Moebus S, Moffatt MF, Mohlke KL, Molony C, Monda KL, Montgomery GW, Mooser V, Morken MA, Morris AD, Morris AP, Mühleisen TW, Müller Nurasyid M, Munroe PB, Musk AW, Narisu N, Navis G, Neale BM, Nelis M, Nemesh J, Neville MJ, Ngwa JS, Nicholson G, Nieminen MS, Njølstad I, Nohr EA, Nolte IM, North KE, Nöthen MM, Nyholt DR, O'Connell JR, Ohlsson C, Oldehinkel AJ, van Ommen GJ, Ong KK, Oostra BA, Ouwehand WH, Palmer CN, Palmer LJ, Palotie A, Paré G, Parker AN, Paternoster L, Pawitan Y, Pechlivanis S, Peden JF, Pedersen NL, Pedersen O, Pellikka N, Peltonen L, Penninx B, Perola M, Perry JR, Person T, Peters A, Peters MJ, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Power C, Pramstaller PP, Preuss M, Price JF, Prokopenko I, Province MA, Psaty BM, Purcell S, Pütter C, Qi L, Quertermous T, Radhakrishnan A, Raitakari O, Randall JC, Rauramaa R, Rayner NW, Rehnberg E, Rendon A, Ridderstråle M, Ridker PM, Ripatti S, Rissanen A, Rivadeneira F, Rivolta C, Robertson NR, Rose LM, Rudan I, Saaristo TE, Sager H, Salomaa V, Samani NJ, Sambrook JG, Sanders AR, Sandholt C, Sanna S, Saramies J, Schadt EE, Scherag A, Schipf S, Schlessinger D, Schreiber S, Schunkert H, Schwarz PE, Scott LJ, Shi J, Shin SY, Shuldiner AR, Shungin D, Signorini S, Silander K, Sinisalo J, Skrobek B, Smit JH, Smith AV, Smith GD, Snieder H, Soranzo N, Sørensen TI, Sovio U, Spector TD, Speliotes EK, Stančáková A, Stark K, Stefansson K, Steinthorsdottir V, Stephens JC, Stirrups K, Stolk RP, Strachan DP, Strawbridge RJ, Stringham HM, Stumvoll M, Surakka I, Swift AJ, Syvanen AC, Tammesoo ML, Teder Laving M, Teslovich TM, Teumer A, Theodoraki EV, Thomson B, Thorand B, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tönjes A, Tregouet DA, Tremoli E, Trip MD, Tuomi T, Tuomilehto J, Tyrer J, Uda M, Uitterlinden AG, Usala G, Uusitupa M, Valle TT, Vandenput L, Vatin V, Vedantam S, de Vegt F, Vermeulen SH, Viikari J, Virtamo J, Visscher PM, Vitart V, Van Vliet Ostaptchouk JV, Voight BF, Vollenweider P, Volpato CB, Völzke H, Waeber G, Waite LL, Wallaschofski H, Walters GB, Wang Z, Wareham NJ, Watanabe RM, Watkins H, Weedon MN, Welch R, Weyant RJ, Wheeler E, White CC, Wichmann HE, Widen E, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, van Wingerden S, Winkelmann BR, Winkler TW, Witte DR, Witteman JC, Wolffenbuttel BH, Wong A, Wood AR, Workalemahu T, Wright AF, Yang J, Yarnell JW, Zgaga L, Zhao JH, Zillikens MC, Zitting P, Zondervan KT, Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis, G, Absher, D, Alavere, H, Albrecht, E, Allen, H, Almgren, P, Amin, N, Amouyel, P, Anderson, D, Arnold, A, Arveiler, D, Aspelund, T, Asselbergs, F, Assimes, T, Atalay, M, Attwood, A, Atwood, L, Bakker, S, Balkau, B, Balmforth, A, Barlassina, C, Barroso, I, Basart, H, Bauer, S, Beckmann, J, Beilby, J, Bennett, A, Ben Shlomo, Y, Bergman, R, Bergmann, S, Berndt, S, Biffar, R, Di Blasio, A, Boehm, B, Boehnke, M, Boeing, H, Boerwinkle, E, Bolton, J, Bonnefond, A, Bonnycastle, L, Boomsma, D, Borecki, I, Bornstein, S, Bouatia Naji, N, Boucher, G, Bragg Gresham, J, Brambilla, P, Bruinenberg, M, Buchanan, T, Buechler, C, Cadby, G, Campbell, H, Caulfield, M, Cavalcanti Proença, C, Cesana, G, Chanock, S, Chasman, D, Chen, Y, Chines, P, Clegg, D, Coin, L, Collins, F, Connell, J, Cookson, W, Cooper, M, Cupples, L, Cusi, D, Day, I, Dedoussis, G, Dei, M, Deloukas, P, Dermitzakis, E, Dimas, A, Dimitriou, M, Dixon, A, Dörr, M, van Duijn, C, Ebrahim, S, Edkins, S, Eiriksdottir, G, Eisinger, K, Eklund, N, Elliott, P, Erbel, R, Erdmann, J, Erdos, M, Eriksson, J, Estrada, K, Evans, D, de Faire, U, Farrall, M, Feitosa, M, Ferrario, M, Ferrières, J, Fischer, K, Fisher, E, Fowkes, G, Fox, C, Franke, L, Franks, P, Fraser, R, Frau, F, Frayling, T, Freimer, N, Froguel, P, Fu, M, Gaget, S, Ganna, A, Gejman, P, Gentilini, D, Geus, E, Gieger, C, Gigante, B, Gjesing, A, Glazer, N, Goddard, M, Goel, A, Grallert, H, Gräßler, J, Grönberg, H, Groop, L, Groves, C, Gudnason, V, Guiducci, C, Gyllensten, U, Hall, A, Hall, P, Hallmans, G, Hamsten, A, Hansen, T, Haritunians, T, Harris, T, van der Harst, P, Hartikainen, A, Hassanali, N, Hattersley, A, Havulinna, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, den Heijer, M, Hengstenberg, C, Herzig, K, Hicks, A, Hingorani, A, Hinney, A, Hirschhorn, J, Hofman, A, Holmes, C, Homuth, G, Hottenga, J, Hovingh, K, Hu, F, Hu, Y, Huffman, J, Hui, J, Huikuri, H, Humphries, S, Hung, J, Hunt, S, Hunter, D, Hveem, K, Hyppönen, E, Igl, W, Illig, T, Ingelsson, E, Iribarren, C, Isomaa, B, Jackson, A, Jacobs, K, James, A, Jansson, J, Jarick, I, Jarvelin, M, Jöckel, K, Johansson, Å, Johnson, T, Jolley, J, Jørgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kähönen, M, Kajantie, E, Kanoni, S, Kao, W, Kaplan, L, Kaplan, R, Kaprio, J, Kapur, K, Karpe, F, Kathiresan, S, Kee, F, Keinanen Kiukaanniemi, S, Ketkar, S, Kettunen, J, Khaw, K, Kiemeney, L, Kinnunen, L, Kivimaki, M, Kivmaki, M, Van der Klauw, M, Kleber, M, Knowles, J, Koenig, W, Kolcic, I, Kolovou, G, König, I, Koskinen, S, Kovacs, P, Kraft, P, Kraja, A, Kristiansson, K, Krjutåjkov, K, Kroemer, H, Krohn, J, Krzelj, V, Kuh, D, Kulzer, J, Kumari, M, Kuulasmaa, K, Kuusisto, J, Kvaloy, K, Laakso, M, Laitinen, J, Lakka, T, Lamina, C, Langenberg, C, Lantieri, O, Lathrop, G, Launer, L, Lawlor, D, Lawrence, R, Leach, I, Lecoeur, C, Lee, S, Lehtimäki, T, Leitzmann, M, Lettre, G, Levinson, D, Li, G, Li, S, Liang, L, Lin, D, Lind, L, Lindgren, C, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Loley, C, Lorentzon, M, Luben, R, Ludwig, B, Madden, P, Magnusson, P, Mangino, M, Manunta, P, Marek, D, Marre, M, Martin, N, März, W, Maschio, A, Mathieson, I, Mcardle, W, Mccaroll, S, Mccarthy, A, Mccarthy, M, Mcknight, B, Medina Gomez, C, Medland, S, Meitinger, T, Metspalu, A, van Meurs, J, Meyre, D, Midthjell, K, Mihailov, E, Milani, L, Min, J, Moebus, S, Moffatt, M, Mohlke, K, Molony, C, Monda, K, Montgomery, G, Mooser, V, Morken, M, Morris, A, Mühleisen, T, Müller Nurasyid, M, Munroe, P, Musk, A, Narisu, N, Navis, G, Neale, B, Nelis, M, Nemesh, J, Neville, M, Ngwa, J, Nicholson, G, Nieminen, M, Njølstad, I, Nohr, E, Nolte, I, North, K, Nöthen, M, Nyholt, D, O'Connell, J, Ohlsson, C, Oldehinkel, A, van Ommen, G, Ong, K, Oostra, B, Ouwehand, W, Palmer, C, Palmer, L, Palotie, A, Paré, G, Parker, A, Paternoster, L, Pawitan, Y, Pechlivanis, S, Peden, J, Pedersen, N, Pedersen, O, Pellikka, N, Peltonen, L, Penninx, B, Perola, M, Perry, J, Person, T, Peters, A, Peters, M, Pichler, I, Pietiläinen, K, Platou, C, Polasek, O, Pouta, A, Power, C, Pramstaller, P, Preuss, M, Price, J, Prokopenko, I, Province, M, Psaty, B, Purcell, S, Pütter, C, Qi, L, Quertermous, T, Radhakrishnan, A, Raitakari, O, Rauramaa, R, Rayner, N, Rehnberg, E, Rendon, A, Ridderstråle, M, Ridker, P, Ripatti, S, Rissanen, A, Rivadeneira, F, Rivolta, C, Robertson, N, Rose, L, Rudan, I, Saaristo, T, Sager, H, Salomaa, V, Samani, N, Sambrook, J, Sanders, A, Sandholt, C, Sanna, S, Saramies, J, Schadt, E, Schipf, S, Schlessinger, D, Schreiber, S, Schunkert, H, Schwarz, P, Scott, L, Shi, J, Shin, S, Shuldiner, A, Shungin, D, Signorini, S, Silander, K, Sinisalo, J, Skrobek, B, Smit, J, Smith, A, Smith, G, Snieder, H, Soranzo, N, Sørensen, T, Sovio, U, Spector, T, Speliotes, E, Stančáková, A, Stark, K, Stefansson, K, Steinthorsdottir, V, Stephens, J, Stirrups, K, Stolk, R, Strachan, D, Strawbridge, R, Stringham, H, Stumvoll, M, Surakka, I, Swift, A, Syvanen, A, Tammesoo, M, Teder Laving, M, Teslovich, T, Teumer, A, Theodoraki, E, Thomson, B, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Timpson, N, Tönjes, A, Tregouet, D, Tremoli, E, Trip, M, Tuomi, T, Tuomilehto, J, Tyrer, J, Uda, M, Uitterlinden, A, Usala, G, Uusitupa, M, Valle, T, Vandenput, L, Vatin, V, de Vegt, F, Vermeulen, S, Viikari, J, Virtamo, J, Visscher, P, Vitart, V, Van Vliet Ostaptchouk, J, Voight, B, Vollenweider, P, Volpato, C, Völzke, H, Waeber, G, Waite, L, Wallaschofski, H, Walters, G, Wang, Z, Wareham, N, Watanabe, R, Watkins, H, Weedon, M, Welch, R, Weyant, R, Wheeler, E, White, C, Wichmann, H, Widen, E, Wild, S, Willemsen, G, Willer, C, Wilsgaard, T, Wilson, J, van Wingerden, S, Winkelmann, B, Witte, D, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Yang, J, Yarnell, J, Zgaga, L, Zhao, J, Zillikens, M, Zitting, P, Zondervan, K, Abecasis GR, Absher D, Alavere H, Albrecht E, Allen HL, Almgren P, Amin N, Amouyel P, Anderson D, Arnold AM, Arveiler D, Aspelund T, Asselbergs FW, Assimes TL, Atalay M, Attwood AP, Atwood LD, Bakker SJ, Balkau B, Balmforth AJ, Barlassina C, Barroso I, Basart H, Bauer S, Beckmann JS, Beilby JP, Bennett AJ, Ben Shlomo Y, Bergman RN, Bergmann S, Berndt SI, Biffar R, Di Blasio AM, Boehm BO, Boehnke M, Boeing H, Boerwinkle E, Bolton JL, Bonnefond A, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bouatia Naji N, Boucher G, Bragg Gresham JL, BRAMBILLA, PAOLO, Bruinenberg M, Buchanan TA, Buechler C, Cadby G, Campbell H, Caulfield MJ, Cavalcanti Proença C, CESANA, GIANCARLO, Chanock SJ, Chasman DI, Chen YD, Chines PS, Clegg DJ, Coin L, Collins FS, Connell JM, Cookson W, Cooper MN, Croteau Chonka DC, Cupples LA, Cusi D, Day FR, Day IN, Dedoussis GV, Dei M, Deloukas P, Dermitzakis ET, Dimas AS, Dimitriou M, Dixon AL, Dörr M, van Duijn CM, Ebrahim S, Edkins S, Eiriksdottir G, Eisinger K, Eklund N, Elliott P, Erbel R, Erdmann J, Erdos MR, Eriksson JG, Esko T, Estrada K, Evans DM, de Faire U, Fall T, Farrall M, Feitosa MF, Ferrario MM, Ferreira T, Ferrières J, Fischer K, Fisher E, Fowkes G, Fox CS, Franke L, Franks PW, Fraser RM, Frau F, Frayling T, Freimer NB, Froguel P, Fu M, Gaget S, Ganna A, Gejman PV, Gentilini D, Geus EJ, Gieger C, Gigante B, Gjesing AP, Glazer NL, Goddard ME, Goel A, Grallert H, Gräßler J, Grönberg H, Groop LC, Groves CJ, Gudnason V, Guiducci C, Gustafsson S, Gyllensten U, Hall AS, Hall P, Hallmans G, Hamsten A, Hansen T, Haritunians T, Harris TB, van der Harst P, Hartikainen AL, Hassanali N, Hattersley AT, Havulinna AS, Hayward C, Heard Costa NL, Heath AC, Hebebrand J, Heid IM, den Heijer M, Hengstenberg C, Herzig KH, Hicks AA, Hingorani A, Hinney A, Hirschhorn JN, Hofman A, Holmes CC, Homuth G, Hottenga JJ, Hovingh KG, Hu FB, Hu YJ, Huffman JE, Hui J, Huikuri H, Humphries SE, Hung J, Hunt SE, Hunter D, Hveem K, Hyppönen E, Igl W, Illig T, Ingelsson E, Iribarren C, Isomaa B, Jackson AU, Jacobs KB, James AL, Jansson JO, Jarick I, Jarvelin MR, Jöckel KH, Johansson Å, Johnson T, Jolley J, Jørgensen T, Jousilahti P, Jula A, Justice AE, Kaakinen M, Kähönen M, Kajantie E, Kanoni S, Kao WH, Kaplan LM, Kaplan RC, Kaprio J, Kapur K, Karpe F, Kathiresan S, Kee F, Keinanen Kiukaanniemi SM, Ketkar S, Kettunen J, Khaw KT, Kiemeney LA, Kilpeläinen TO, Kinnunen L, Kivimaki M, Kivmaki M, Van der Klauw MM, Kleber ME, Knowles JW, Koenig W, Kolcic I, Kolovou G, König IR, Koskinen S, Kovacs P, Kraft P, Kraja AT, Kristiansson K, KrjutÅjkov K, Kroemer HK, Krohn JP, Krzelj V, Kuh D, Kulzer JR, Kumari M, Kutalik Z, Kuulasmaa K, Kuusisto J, Kvaloy K, Laakso M, Laitinen JH, Lakka TA, Lamina C, Langenberg C, Lantieri O, Lathrop GM, Launer LJ, Lawlor DA, Lawrence RW, Leach IM, Lecoeur C, Lee SH, Lehtimäki T, Leitzmann MF, Lettre G, Levinson DF, Li G, Li S, Liang L, Lin DY, Lind L, Lindgren CM, Lindström J, Liu J, Liuzzi A, Locke AE, Lokki ML, Loley C, Loos RJ, Lorentzon M, Luan J, Luben RN, Ludwig B, Madden PA, Mägi R, Magnusson PK, Mangino M, Manunta P, Marek D, Marre M, Martin NG, März W, Maschio A, Mathieson I, McArdle WL, McCaroll SA, McCarthy A, McCarthy MI, McKnight B, Medina Gomez C, Medland SE, Meitinger T, Metspalu A, van Meurs JB, Meyre D, Midthjell K, Mihailov E, Milani L, Min JL, Moebus S, Moffatt MF, Mohlke KL, Molony C, Monda KL, Montgomery GW, Mooser V, Morken MA, Morris AD, Morris AP, Mühleisen TW, Müller Nurasyid M, Munroe PB, Musk AW, Narisu N, Navis G, Neale BM, Nelis M, Nemesh J, Neville MJ, Ngwa JS, Nicholson G, Nieminen MS, Njølstad I, Nohr EA, Nolte IM, North KE, Nöthen MM, Nyholt DR, O'Connell JR, Ohlsson C, Oldehinkel AJ, van Ommen GJ, Ong KK, Oostra BA, Ouwehand WH, Palmer CN, Palmer LJ, Palotie A, Paré G, Parker AN, Paternoster L, Pawitan Y, Pechlivanis S, Peden JF, Pedersen NL, Pedersen O, Pellikka N, Peltonen L, Penninx B, Perola M, Perry JR, Person T, Peters A, Peters MJ, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Power C, Pramstaller PP, Preuss M, Price JF, Prokopenko I, Province MA, Psaty BM, Purcell S, Pütter C, Qi L, Quertermous T, Radhakrishnan A, Raitakari O, Randall JC, Rauramaa R, Rayner NW, Rehnberg E, Rendon A, Ridderstråle M, Ridker PM, Ripatti S, Rissanen A, Rivadeneira F, Rivolta C, Robertson NR, Rose LM, Rudan I, Saaristo TE, Sager H, Salomaa V, Samani NJ, Sambrook JG, Sanders AR, Sandholt C, Sanna S, Saramies J, Schadt EE, Scherag A, Schipf S, Schlessinger D, Schreiber S, Schunkert H, Schwarz PE, Scott LJ, Shi J, Shin SY, Shuldiner AR, Shungin D, Signorini S, Silander K, Sinisalo J, Skrobek B, Smit JH, Smith AV, Smith GD, Snieder H, Soranzo N, Sørensen TI, Sovio U, Spector TD, Speliotes EK, Stančáková A, Stark K, Stefansson K, Steinthorsdottir V, Stephens JC, Stirrups K, Stolk RP, Strachan DP, Strawbridge RJ, Stringham HM, Stumvoll M, Surakka I, Swift AJ, Syvanen AC, Tammesoo ML, Teder Laving M, Teslovich TM, Teumer A, Theodoraki EV, Thomson B, Thorand B, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tönjes A, Tregouet DA, Tremoli E, Trip MD, Tuomi T, Tuomilehto J, Tyrer J, Uda M, Uitterlinden AG, Usala G, Uusitupa M, Valle TT, Vandenput L, Vatin V, Vedantam S, de Vegt F, Vermeulen SH, Viikari J, Virtamo J, Visscher PM, Vitart V, Van Vliet Ostaptchouk JV, Voight BF, Vollenweider P, Volpato CB, Völzke H, Waeber G, Waite LL, Wallaschofski H, Walters GB, Wang Z, Wareham NJ, Watanabe RM, Watkins H, Weedon MN, Welch R, Weyant RJ, Wheeler E, White CC, Wichmann HE, Widen E, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, van Wingerden S, Winkelmann BR, Winkler TW, Witte DR, Witteman JC, Wolffenbuttel BH, Wong A, Wood AR, Workalemahu T, Wright AF, Yang J, Yarnell JW, Zgaga L, Zhao JH, Zillikens MC, Zitting P, and Zondervan KT
Abstract: Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.
Published: 2014

41. Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes

Author: Albrechtsen, A., Grarup, N., Li, Y., Sparso, T., Tian, G., Cao, H., Jiang, T., Kim, S. Y., Korneliussen, T., Li, Q., Nie, C., Wu, R., Skotte, L., Morris, A. P., Ladenvall, C., Cauchi, S., Stancakova, A., Andersen, G., Astrup, A., Banasik, K., Bennett, A. J., Bolund, L., Charpentier, G., Chen, Y., Dekker, J. M., Doney, A. S. F., Dorkhan, M., Forsen, T., Frayling, T. M., Groves, C. J., Gui, Y., Hallmans, Göran, Hattersley, A. T., He, K., Hitman, G. A., Holmkvist, J., Huang, S., Jiang, H., Jin, X., Justesen, J. M., Kristiansen, K., Kuusisto, J., Lajer, M., Lantieri, O., Li, W., Liang, H., Liao, Q., Liu, X., Ma, T., Ma, X., Manijak, M. P., Marre, M., Mokrosinski, J., Morris, A. D., Mu, B., Nielsen, A. A., Nijpels, G., Nilsson, P., Palmer, C. N. A., Rayner, N. W., Renstrom, F., Ribel-Madsen, R., Robertson, N., Rolandsson, Olov, Rossing, P., Schwartz, T. W., Slagboom, P. E., Sterner, M., Tang, M., Tarnow, L., Tuomi, T., van't Riet, E., van Leeuwen, N., Varga, T. V., Vestmar, M. A., Walker, M., Wang, B., Wang, Y., Wu, H., Xi, F., Yengo, L., Yu, C., Zhang, X., Zhang, J., Zhang, Q., Zhang, W., Zheng, H., Zhou, Y., Altshuler, D., 't Hart, L. M., Franks, Paul W., Balkau, B., Froguel, P., McCarthy, M. I., Laakso, M., Groop, L., Christensen, C., Brandslund, I., Lauritzen, T., Witte, D. R., Linneberg, A., Jorgensen, T., Hansen, T., Wang, J., Nielsen, R., Pedersen, O., Albrechtsen, A., Grarup, N., Li, Y., Sparso, T., Tian, G., Cao, H., Jiang, T., Kim, S. Y., Korneliussen, T., Li, Q., Nie, C., Wu, R., Skotte, L., Morris, A. P., Ladenvall, C., Cauchi, S., Stancakova, A., Andersen, G., Astrup, A., Banasik, K., Bennett, A. J., Bolund, L., Charpentier, G., Chen, Y., Dekker, J. M., Doney, A. S. F., Dorkhan, M., Forsen, T., Frayling, T. M., Groves, C. J., Gui, Y., Hallmans, Göran, Hattersley, A. T., He, K., Hitman, G. A., Holmkvist, J., Huang, S., Jiang, H., Jin, X., Justesen, J. M., Kristiansen, K., Kuusisto, J., Lajer, M., Lantieri, O., Li, W., Liang, H., Liao, Q., Liu, X., Ma, T., Ma, X., Manijak, M. P., Marre, M., Mokrosinski, J., Morris, A. D., Mu, B., Nielsen, A. A., Nijpels, G., Nilsson, P., Palmer, C. N. A., Rayner, N. W., Renstrom, F., Ribel-Madsen, R., Robertson, N., Rolandsson, Olov, Rossing, P., Schwartz, T. W., Slagboom, P. E., Sterner, M., Tang, M., Tarnow, L., Tuomi, T., van't Riet, E., van Leeuwen, N., Varga, T. V., Vestmar, M. A., Walker, M., Wang, B., Wang, Y., Wu, H., Xi, F., Yengo, L., Yu, C., Zhang, X., Zhang, J., Zhang, Q., Zhang, W., Zheng, H., Zhou, Y., Altshuler, D., 't Hart, L. M., Franks, Paul W., Balkau, B., Froguel, P., McCarthy, M. I., Laakso, M., Groop, L., Christensen, C., Brandslund, I., Lauritzen, T., Witte, D. R., Linneberg, A., Jorgensen, T., Hansen, T., Wang, J., Nielsen, R., and Pedersen, O.
Abstract: Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
Published: 2013
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42. Small noncoding differentially methylated copy-number variants, including IncRNA genes, cause a lethal lung developmental disorder

Author: Szafranski, P. (Przemyslaw), Dharmadhikari, A.V. (Avinash), Brosens, E. (Erwin), Gurha, P. (Priyatansh), Kołodziejska, K.E. (Katarzyna), Zhishuo, O. (Ou), Dittwald, P. (Piotr), Majewski, J. (Jacek), Mohan, K.N. (K. Naga), Chen, B.P.C. (Benjamin), Person, A.D. (Anthony), Tibboel, D. (Dick), Klein, J.E.M.M. (Annelies) de, Pinner, J. (Jason), Chopra PhD, M. (Mickey), Malcolm, G. (Girvan), Peters, G., Arbuckle, S. (Susan), Guiang III, S.F. (Sixto), Hustead, V.A. (Virginia), Jessurun, J. (Jose), Hirsch, R. (Russel), Witte, D. (David), Maystadt, I. (Isabelle), Sebire, N. (Neil), Fisher, R. (Rachel), Langston, C. (Claire), Sen, P. (Partha), Stankiewicz, P. (Paweł), Szafranski, P. (Przemyslaw), Dharmadhikari, A.V. (Avinash), Brosens, E. (Erwin), Gurha, P. (Priyatansh), Kołodziejska, K.E. (Katarzyna), Zhishuo, O. (Ou), Dittwald, P. (Piotr), Majewski, J. (Jacek), Mohan, K.N. (K. Naga), Chen, B.P.C. (Benjamin), Person, A.D. (Anthony), Tibboel, D. (Dick), Klein, J.E.M.M. (Annelies) de, Pinner, J. (Jason), Chopra PhD, M. (Mickey), Malcolm, G. (Girvan), Peters, G., Arbuckle, S. (Susan), Guiang III, S.F. (Sixto), Hustead, V.A. (Virginia), Jessurun, J. (Jose), Hirsch, R. (Russel), Witte, D. (David), Maystadt, I. (Isabelle), Sebire, N. (Neil), Fisher, R. (Rachel), Langston, C. (Claire), Sen, P. (Partha), and Stankiewicz, P. (Paweł)
Abstract: An unanticipated and tremendous amount of the noncoding sequence of the human genome is transcribed. Long noncoding RNAs (IncRNAs) constitute a significant fraction of non-protein-coding transcripts; however, their functions remain enigmatic. We demonstrate that deletions of a small noncoding differentially methylated region at 16q24.1, including IncRNA genes, cause a lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), with parent-of-origin effects. We identify overlapping deletions 250 kb upstream of FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete lung-specific IncRNAgenes. These deletions define a distant cis-regulatory region that harbors, besides lncRNAgenes, also a differentially methylated CpGisland, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter. Wesuggest that lung-transcribed 16q24.1 IncRNAs may contribute to long-range regulation of FOXF1 by GLI2 and other transcription factors. Perturbation of IncRNA-mediated chromatin interactions may, in general, be responsible for position effect phenomena and potentially cause many disorders of human development.
Published: 2013
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43. The Extended Enterprise Coherence-Governance Assessment

Author: Aier, S., Ekstedt, M., Matthes, F., Proper, E., Sanz, J., Wagter, R., Proper, H.A., Witte, D., Aier, S., Ekstedt, M., Matthes, F., Proper, E., Sanz, J., Wagter, R., Proper, H.A., and Witte, D.
Abstract: Item does not contain fulltext
Published: 2012

44. A Practice-Based Framework for Enterprise Coherence

Author: Proper, E., Wagter, R., Proper, H.A., Witte, D., Proper, E., Wagter, R., Proper, H.A., and Witte, D.
Abstract: Contains fulltext : 103233.pdf (publisher's version ) (Closed access)
Published: 2012

45. Enterprise Coherence in the Dutch Ministry of Social Affairs and Employment

Author: Bajec, M., Eder, J., Wagter, R., Proper, H.A., Witte, D., Bajec, M., Eder, J., Wagter, R., Proper, H.A., and Witte, D.
Abstract: Item does not contain fulltext
Published: 2012

46. On the Use of GEA at the Dutch Ministry of Social Affairs and Employment

Author: Wagter, R., Proper, H.A., Witte, D., Wagter, R., Proper, H.A., and Witte, D.
Abstract: 09 september 2012, Item does not contain fulltext
Published: 2012

47. The Extended Enterprise Coherence-Governance Assessment

Author: Aier, S., Ekstedt, M., Matthes, F., Proper, E., Sanz, J., Wagter, R., Proper, H.A., Witte, D., Aier, S., Ekstedt, M., Matthes, F., Proper, E., Sanz, J., Wagter, R., Proper, H.A., and Witte, D.
Abstract: Item does not contain fulltext
Published: 2012

48. A Practice-Based Framework for Enterprise Coherence

Author: Proper, E., Wagter, R., Proper, H.A., Witte, D., Proper, E., Wagter, R., Proper, H.A., and Witte, D.
Abstract: Contains fulltext : 103233.pdf (publisher's version ) (Closed access)
Published: 2012

49. Enterprise Coherence in the Dutch Ministry of Social Affairs and Employment

Author: Bajec, M., Eder, J., Wagter, R., Proper, H.A., Witte, D., Bajec, M., Eder, J., Wagter, R., Proper, H.A., and Witte, D.
Abstract: Item does not contain fulltext
Published: 2012

50. On the Use of GEA at the Dutch Ministry of Social Affairs and Employment

Author: Wagter, R., Proper, H.A., Witte, D., Wagter, R., Proper, H.A., and Witte, D.
Abstract: 2012 IEEE 14th International Conference on Commerce and Enterprise Computing (CEC), 09 september 2012, Item does not contain fulltext
Published: 2012

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