1,025 results on '"Witte, Daniel R."'
Search Results
2. Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health
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Stankevic, Evelina, Kern, Timo, Borisevich, Dmitrii, Poulsen, Casper Sahl, Madsen, Anne Lundager, Hansen, Tue Haldor, Jonsson, Anna, Schubert, Mikkel, Nygaard, Nikoline, Nielsen, Trine, Belstrøm, Daniel, Ahluwalia, Tarunveer S., Witte, Daniel R., Grarup, Niels, Arumugam, Manimozhiyan, Pedersen, Oluf, and Hansen, Torben
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- 2024
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3. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology
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Suzuki, Ken, Hatzikotoulas, Konstantinos, Southam, Lorraine, Taylor, Henry J., Yin, Xianyong, Lorenz, Kim M., Mandla, Ravi, Huerta-Chagoya, Alicia, Melloni, Giorgio E. M., Kanoni, Stavroula, Rayner, Nigel W., Bocher, Ozvan, Arruda, Ana Luiza, Sonehara, Kyuto, Namba, Shinichi, Lee, Simon S. K., Preuss, Michael H., Petty, Lauren E., Schroeder, Philip, Vanderwerff, Brett, Kals, Mart, Bragg, Fiona, Lin, Kuang, Guo, Xiuqing, Zhang, Weihua, Yao, Jie, Kim, Young Jin, Graff, Mariaelisa, Takeuchi, Fumihiko, Nano, Jana, Lamri, Amel, Nakatochi, Masahiro, Moon, Sanghoon, Scott, Robert A., Cook, James P., Lee, Jung-Jin, Pan, Ian, Taliun, Daniel, Parra, Esteban J., Chai, Jin-Fang, Bielak, Lawrence F., Tabara, Yasuharu, Hai, Yang, Thorleifsson, Gudmar, Grarup, Niels, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloé, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Kwak, Soo-Heon, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Nongmaithem, Suraj S., Noordam, Raymond, Lim, Victor J. Y., Tam, Claudia H. T., Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M., Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R., Chen, Guanjie, Brody, Jennifer A., Kabagambe, Edmond, An, Ping, Xiang, Anny H., Choi, Hyeok Sun, Cade, Brian E., Tan, Jingyi, Broadaway, K. Alaine, Williamson, Alice, Kamali, Zoha, Cui, Jinrui, Thangam, Manonanthini, Adair, Linda S., Adeyemo, Adebowale, Aguilar-Salinas, Carlos A., Ahluwalia, Tarunveer S., Anand, Sonia S., Bertoni, Alain, Bork-Jensen, Jette, Brandslund, Ivan, Buchanan, Thomas A., Burant, Charles F., Butterworth, Adam S., Canouil, Mickaël, Chan, Juliana C. N., Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Cushman, Mary, Danesh, John, Das, Swapan K., de Silva, H. Janaka, Dedoussis, George, Dimitrov, Latchezar, Doumatey, Ayo P., Du, Shufa, Duan, Qing, Eckardt, Kai-Uwe, Emery, Leslie S., Evans, Daniel S., Evans, Michele K., Fischer, Krista, Floyd, James S., Ford, Ian, Franco, Oscar H., Frayling, Timothy M., Freedman, Barry I., Genter, Pauline, Gerstein, Hertzel C., Giedraitis, Vilmantas, González-Villalpando, Clicerio, González-Villalpando, Maria Elena, Gordon-Larsen, Penny, Gross, Myron, Guare, Lindsay A., Hackinger, Sophie, Hakaste, Liisa, Han, Sohee, Hattersley, Andrew T., Herder, Christian, Horikoshi, Momoko, Howard, Annie-Green, Hsueh, Willa, Huang, Mengna, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Ikram, Mohammad Arfan, Ingelsson, Martin, Islam, Md. Tariqul, Isono, Masato, Jang, Hye-Mi, Jasmine, Farzana, Jiang, Guozhi, Jonas, Jost B., Jørgensen, Torben, Kamanu, Frederick K., Kandeel, Fouad R., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kaur, Varinderpal, Kawaguchi, Takahisa, Keaton, Jacob M., Kho, Abel N., Khor, Chiea-Chuen, Kibriya, Muhammad G., Kim, Duk-Hwan, Kronenberg, Florian, Kuusisto, Johanna, Läll, Kristi, Lange, Leslie A., Lee, Kyung Min, Lee, Myung-Shik, Lee, Nanette R., Leong, Aaron, Li, Liming, Li, Yun, Li-Gao, Ruifang, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Locke, Adam E., Louie, Tin, Luan, Jian’an, Luk, Andrea O., Luo, Xi, Lv, Jun, Lynch, Julie A., Lyssenko, Valeriya, Maeda, Shiro, Mamakou, Vasiliki, Mansuri, Sohail Rafik, Matsuda, Koichi, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mo, Huan, Morris, Andrew D., Moura, Filipe A., Nadler, Jerry L., Nalls, Michael A., Nayak, Uma, Ntalla, Ioanna, Okada, Yukinori, Orozco, Lorena, Patel, Sanjay R., Patil, Snehal, Pei, Pei, Pereira, Mark A., Peters, Annette, Pirie, Fraser J., Polikowsky, Hannah G., Porneala, Bianca, Prasad, Gauri, Rasmussen-Torvik, Laura J., Reiner, Alexander P., Roden, Michael, Rohde, Rebecca, Roll, Katheryn, Sabanayagam, Charumathi, Sandow, Kevin, Sankareswaran, Alagu, Sattar, Naveed, Schönherr, Sebastian, Shahriar, Mohammad, Shen, Botong, Shi, Jinxiu, Shin, Dong Mun, Shojima, Nobuhiro, Smith, Jennifer A., So, Wing Yee, Stančáková, Alena, Steinthorsdottir, Valgerdur, Stilp, Adrienne M., Strauch, Konstantin, Taylor, Kent D., Thorand, Barbara, Thorsteinsdottir, Unnur, Tomlinson, Brian, Tran, Tam C., Tsai, Fuu-Jen, Tuomilehto, Jaakko, Tusie-Luna, Teresa, Udler, Miriam S., Valladares-Salgado, Adan, van Dam, Rob M., van Klinken, Jan B., Varma, Rohit, Wacher-Rodarte, Niels, Wheeler, Eleanor, Wickremasinghe, Ananda R., van Dijk, Ko Willems, Witte, Daniel R., Yajnik, Chittaranjan S., Yamamoto, Ken, Yamamoto, Kenichi, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Yusuf, Salim, Zawistowski, Matthew, Zhang, Liang, Zheng, Wei, Raffel, Leslie J., Igase, Michiya, Ipp, Eli, Redline, Susan, Cho, Yoon Shin, Lind, Lars, Province, Michael A., Fornage, Myriam, Hanis, Craig L., Ingelsson, Erik, Zonderman, Alan B., Psaty, Bruce M., Wang, Ya-Xing, Rotimi, Charles N., Becker, Diane M., Matsuda, Fumihiko, Liu, Yongmei, Yokota, Mitsuhiro, Kardia, Sharon L. R., Peyser, Patricia A., Pankow, James S., Engert, James C., Bonnefond, Amélie, Froguel, Philippe, Wilson, James G., Sheu, Wayne H. H., Wu, Jer-Yuarn, Hayes, M. Geoffrey, Ma, Ronald C. W., Wong, Tien-Yin, Mook-Kanamori, Dennis O., Tuomi, Tiinamaija, Chandak, Giriraj R., Collins, Francis S., Bharadwaj, Dwaipayan, Paré, Guillaume, Sale, Michèle M., Ahsan, Habibul, Motala, Ayesha A., Shu, Xiao-Ou, Park, Kyong-Soo, Jukema, J. Wouter, Cruz, Miguel, Chen, Yii-Der Ida, Rich, Stephen S., McKean-Cowdin, Roberta, Grallert, Harald, Cheng, Ching-Yu, Ghanbari, Mohsen, Tai, E-Shyong, Dupuis, Josee, Kato, Norihiro, Laakso, Markku, Köttgen, Anna, Koh, Woon-Puay, Bowden, Donald W., Palmer, Colin N. A., Kooner, Jaspal S., Kooperberg, Charles, Liu, Simin, North, Kari E., Saleheen, Danish, Hansen, Torben, Pedersen, Oluf, Wareham, Nicholas J., Lee, Juyoung, Kim, Bong-Jo, Millwood, Iona Y., Walters, Robin G., Stefansson, Kari, Ahlqvist, Emma, Goodarzi, Mark O., Mohlke, Karen L., Langenberg, Claudia, Haiman, Christopher A., Loos, Ruth J. F., Florez, Jose C., Rader, Daniel J., Ritchie, Marylyn D., Zöllner, Sebastian, Mägi, Reedik, Marston, Nicholas A., Ruff, Christian T., van Heel, David A., Finer, Sarah, Denny, Joshua C., Yamauchi, Toshimasa, Kadowaki, Takashi, Chambers, John C., Ng, Maggie C. Y., Sim, Xueling, Below, Jennifer E., Tsao, Philip S., Chang, Kyong-Mi, McCarthy, Mark I., Meigs, James B., Mahajan, Anubha, Spracklen, Cassandra N., Mercader, Josep M., Boehnke, Michael, Rotter, Jerome I., Vujkovic, Marijana, Voight, Benjamin F., Morris, Andrew P., and Zeggini, Eleftheria
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- 2024
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4. Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
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Williamson, Alice, Norris, Dougall M, Yin, Xianyong, Broadaway, K Alaine, Moxley, Anne H, Vadlamudi, Swarooparani, Wilson, Emma P, Jackson, Anne U, Ahuja, Vasudha, Andersen, Mette K, Arzumanyan, Zorayr, Bonnycastle, Lori L, Bornstein, Stefan R, Bretschneider, Maxi P, Buchanan, Thomas A, Chang, Yi-Cheng, Chuang, Lee-Ming, Chung, Ren-Hua, Clausen, Tine D, Damm, Peter, Delgado, Graciela E, de Mello, Vanessa D, Dupuis, Josée, Dwivedi, Om P, Erdos, Michael R, Silva, Lilian Fernandes, Frayling, Timothy M, Gieger, Christian, Goodarzi, Mark O, Guo, Xiuqing, Gustafsson, Stefan, Hakaste, Liisa, Hammar, Ulf, Hatem, Gad, Herrmann, Sandra, Højlund, Kurt, Horn, Katrin, Hsueh, Willa A, Hung, Yi-Jen, Hwu, Chii-Min, Jonsson, Anna, Kårhus, Line L, Kleber, Marcus E, Kovacs, Peter, Lakka, Timo A, Lauzon, Marie, Lee, I-Te, Lindgren, Cecilia M, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Luan, Jian’an, Aly, Dina Mansour, Mathiesen, Elisabeth, Moissl, Angela P, Morris, Andrew P, Narisu, Narisu, Perakakis, Nikolaos, Peters, Annette, Prasad, Rashmi B, Rodionov, Roman N, Roll, Kathryn, Rundsten, Carsten F, Sarnowski, Chloé, Savonen, Kai, Scholz, Markus, Sharma, Sapna, Stinson, Sara E, Suleman, Sufyan, Tan, Jingyi, Taylor, Kent D, Uusitupa, Matti, Vistisen, Dorte, Witte, Daniel R, Walther, Romy, Wu, Peitao, Xiang, Anny H, Zethelius, Björn, Ahlqvist, Emma, Bergman, Richard N, Chen, Yii-Der Ida, Collins, Francis S, Fall, Tove, Florez, Jose C, Fritsche, Andreas, Grallert, Harald, Groop, Leif, Hansen, Torben, Koistinen, Heikki A, Komulainen, Pirjo, Laakso, Markku, Lind, Lars, Loeffler, Markus, März, Winfried, Meigs, James B, Raffel, Leslie J, Rauramaa, Rainer, Rotter, Jerome I, Schwarz, Peter EH, and Stumvoll, Michael
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Biochemistry and Cell Biology ,Genetics ,Biological Sciences ,Diabetes ,Clinical Research ,Human Genome ,Prevention ,Nutrition ,2.1 Biological and endogenous factors ,Aetiology ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Metabolic and endocrine ,Humans ,Insulin ,Genome-Wide Association Study ,Insulin Resistance ,Diabetes Mellitus ,Type 2 ,Glucose ,Blood Glucose ,Meta-Analysis of Glucose and Insulin-related Traits Consortium ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P
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- 2023
5. Longitudinal HbA1c patterns before the first treatment of diabetes in routine clinical practice: A latent class trajectory analysis
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Nicolaisen, Sia Kromann, le Cessie, Saskia, Thomsen, Reimar Wernich, Witte, Daniel R., Dekkers, Olaf M., Sørensen, Henrik Toft, and Pedersen, Lars
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- 2024
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6. Genetic insights into resting heart rate and its role in cardiovascular disease
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van de Vegte, Yordi J., Eppinga, Ruben N., van der Ende, M. Yldau, Hagemeijer, Yanick P., Mahendran, Yuvaraj, Salfati, Elias, Smith, Albert V., Tan, Vanessa Y., Arking, Dan E., Ntalla, Ioanna, Appel, Emil V., Schurmann, Claudia, Brody, Jennifer A., Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing Hua, Isaacs, Aaron, Wang, Lihua, Luan, Jian’an, Hwang, Shih-Jen, Mononen, Nina, Auro, Kirsi, Jackson, Anne U., Bielak, Lawrence F., Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Müller-Nurasyid, Martina, Roselli, Carolina, Zhang, Weihua, Kleber, Marcus E., Guo, Xiuqing, Lin, Henry J., Pavani, Francesca, Galesloot, Tessel E., Noordam, Raymond, Milaneschi, Yuri, Schraut, Katharina E., den Hoed, Marcel, Degenhardt, Frauke, Trompet, Stella, van den Berg, Marten E., Pistis, Giorgio, Tham, Yih-Chung, Weiss, Stefan, Sim, Xueling S., Li, Hengtong L., van der Most, Peter J., Nolte, Ilja M., Lyytikäinen, Leo-Pekka, Said, M. Abdullah, Witte, Daniel R., Iribarren, Carlos, Launer, Lenore, Ring, Susan M., de Vries, Paul S., Sever, Peter, Linneberg, Allan, Bottinger, Erwin P., Padmanabhan, Sandosh, Psaty, Bruce M., Sotoodehnia, Nona, Kolcic, Ivana, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Balkau, Beverley, Silva, Claudia T., Newton-Cheh, Christopher H., Nikus, Kjell, Salo, Perttu, Mohlke, Karen L., Peyser, Patricia A., Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari, Rao, Dabeeru C., Cornelis, Marilyn C., Faul, Jessica D., Smith, Jennifer A., Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria Pina, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie, Sinner, Moritz F., Strauch, Konstantin, Delgado, Graciela E., Taylor, Kent D., Yao, Jie, Foco, Luisa, Melander, Olle, de Graaf, Jacqueline, de Mutsert, Renée, de Geus, Eco J. C., Johansson, Åsa, Joshi, Peter K., Lind, Lars, Franke, Andre, Macfarlane, Peter W., Tarasov, Kirill V., Tan, Nicholas, Felix, Stephan B., Tai, E-Shyong, Quek, Debra Q., Snieder, Harold, Ormel, Johan, Ingelsson, Martin, Lindgren, Cecilia, Morris, Andrew P., Raitakari, Olli T., Hansen, Torben, Assimes, Themistocles, Gudnason, Vilmundur, Timpson, Nicholas J., Morrison, Alanna C., Munroe, Patricia B., Strachan, David P., Grarup, Niels, Loos, Ruth J. F., Heckbert, Susan R., Vollenweider, Peter, Hayward, Caroline, Stefansson, Kari, Froguel, Philippe, Groop, Leif, Wareham, Nicholas J., van Duijn, Cornelia M., Feitosa, Mary F., O’Donnell, Christopher J., Kähönen, Mika, Perola, Markus, Boehnke, Michael, Kardia, Sharon L. R., Erdmann, Jeanette, Palmer, Colin N. A., Ohlsson, Claes, Porteous, David J., Eriksson, Johan G., Bouchard, Claude, Moebus, Susanne, Kraft, Peter, Weir, David R., Cusi, Daniele, Ferrucci, Luigi, Ulivi, Sheila, Girotto, Giorgia, Correa, Adolfo, Kääb, Stefan, Peters, Annette, Chambers, John C., Kooner, Jaspal S., März, Winfried, Rotter, Jerome I., Hicks, Andrew A., Smith, J. Gustav, Kiemeney, Lambertus A. L. M., Mook-Kanamori, Dennis O., Penninx, Brenda W. J. H., Gyllensten, Ulf, Wilson, James F., Burgess, Stephen, Sundström, Johan, Lieb, Wolfgang, Jukema, J. Wouter, Eijgelsheim, Mark, Lakatta, Edward L. M., Cheng, Ching-Yu, Dörr, Marcus, Wong, Tien-Yin, Sabanayagam, Charumathi, Oldehinkel, Albertine J., Riese, Harriette, Lehtimäki, Terho, Verweij, Niek, and van der Harst, Pim
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- 2023
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7. Autonomic dysfunction is associated with the development of arterial stiffness: the Whitehall II cohort
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Schaarup, Jonas R., Christensen, Martin S., Hulman, Adam, Hansen, Christian S., Vistisen, Dorte, Tabák, Adam G., Witte, Daniel R., and Bjerg, Lasse
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- 2023
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8. Serum neurofilament light chain – A potential biomarker for polyneuropathy in type 2 diabetes?
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Määttä, Laura L., Andersen, Signe T., Parkner, Tina, Hviid, Claus V.B., Bjerg, Lasse, Kural, Mustafa A., Charles, Morten, Søndergaard, Esben, Sandbæk, Annelli, Tankisi, Hatice, Witte, Daniel R., and Jensen, Troels S.
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- 2023
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9. HbA1c-defined prediabetes and progression to type 2 diabetes in Denmark: A population-based study based on routine clinical care laboratory data
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Nicolaisen, Sia Kromann, Pedersen, Lars, Witte, Daniel R., Sørensen, Henrik Toft, and Thomsen, Reimar Wernich
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- 2023
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10. Kidney function and risk of dementia: Observational study, meta-analysis, and two-sample mendelian randomization study
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Kjaergaard, Alisa D., Ellervik, Christina, Witte, Daniel R., Nordestgaard, Børge G., Frikke-Schmidt, Ruth, and Bojesen, Stig E.
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- 2022
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11. Perception of artificial intelligence-based solutions in healthcare among people with and without diabetes: A cross-sectional survey from the health in Central Denmark cohort
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Schaarup, Jonas F.R., Aggarwal, Ravi, Dalsgaard, Else-Marie, Norman, Kasper, Dollerup, Ole Lindgård, Ashrafian, Hutan, Witte, Daniel R., Sandbæk, Annelli, and Hulman, Adam
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- 2023
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12. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
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Flannick, Jason, Mercader, Josep M, Fuchsberger, Christian, Udler, Miriam S, Mahajan, Anubha, Wessel, Jennifer, Teslovich, Tanya M, Caulkins, Lizz, Koesterer, Ryan, Barajas-Olmos, Francisco, Blackwell, Thomas W, Boerwinkle, Eric, Brody, Jennifer A, Centeno-Cruz, Federico, Chen, Ling, Chen, Siying, Contreras-Cubas, Cecilia, Córdova, Emilio, Correa, Adolfo, Cortes, Maria, DeFronzo, Ralph A, Dolan, Lawrence, Drews, Kimberly L, Elliott, Amanda, Floyd, James S, Gabriel, Stacey, Garay-Sevilla, Maria Eugenia, García-Ortiz, Humberto, Gross, Myron, Han, Sohee, Heard-Costa, Nancy L, Jackson, Anne U, Jørgensen, Marit E, Kang, Hyun Min, Kelsey, Megan, Kim, Bong-Jo, Koistinen, Heikki A, Kuusisto, Johanna, Leader, Joseph B, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Lyssenko, Valeriya, Manning, Alisa K, Marcketta, Anthony, Malacara-Hernandez, Juan Manuel, Martínez-Hernández, Angélica, Matsuo, Karen, Mayer-Davis, Elizabeth, Mendoza-Caamal, Elvia, Mohlke, Karen L, Morrison, Alanna C, Ndungu, Anne, Ng, Maggie CY, O’Dushlaine, Colm, Payne, Anthony J, Pihoker, Catherine, Post, Wendy S, Preuss, Michael, Psaty, Bruce M, Vasan, Ramachandran S, Rayner, N William, Reiner, Alexander P, Revilla-Monsalve, Cristina, Robertson, Neil R, Santoro, Nicola, Schurmann, Claudia, So, Wing Yee, Soberón, Xavier, Stringham, Heather M, Strom, Tim M, Tam, Claudia HT, Thameem, Farook, Tomlinson, Brian, Torres, Jason M, Tracy, Russell P, van Dam, Rob M, Vujkovic, Marijana, Wang, Shuai, Welch, Ryan P, Witte, Daniel R, Wong, Tien-Yin, Atzmon, Gil, Barzilai, Nir, Blangero, John, Bonnycastle, Lori L, Bowden, Donald W, Chambers, John C, Chan, Edmund, Cheng, Ching-Yu, Cho, Yoon Shin, Collins, Francis S, de Vries, Paul S, Duggirala, Ravindranath, Glaser, Benjamin, Gonzalez, Clicerio, Gonzalez, Ma Elena, Groop, Leif, Kooner, Jaspal Singh, and Kwak, Soo Heon
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Prevention ,Biotechnology ,Diabetes ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Animals ,Case-Control Studies ,Decision Support Techniques ,Diabetes Mellitus ,Type 2 ,Exome ,Female ,Gene Frequency ,Genome-Wide Association Study ,Humans ,Male ,Mice ,Mice ,Knockout ,Exome Sequencing ,Broad Genomics Platform ,DiscovEHR Collaboration ,CHARGE ,LuCamp ,ProDiGY ,GoT2D ,ESP ,SIGMA-T2D ,T2D-GENES ,AMP-T2D-GENES ,General Science & Technology - Abstract
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10-3) and candidate genes from knockout mice (P = 5.2 × 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.
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- 2019
13. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
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Mahajan, Anubha, Spracklen, Cassandra N., Zhang, Weihua, Ng, Maggie C. Y., Petty, Lauren E., Kitajima, Hidetoshi, Yu, Grace Z., Rüeger, Sina, Speidel, Leo, Kim, Young Jin, Horikoshi, Momoko, Mercader, Josep M., Taliun, Daniel, Moon, Sanghoon, Kwak, Soo-Heon, Robertson, Neil R., Rayner, Nigel W., Loh, Marie, Kim, Bong-Jo, Chiou, Joshua, Miguel-Escalada, Irene, della Briotta Parolo, Pietro, Lin, Kuang, Bragg, Fiona, Preuss, Michael H., Takeuchi, Fumihiko, Nano, Jana, Guo, Xiuqing, Lamri, Amel, Nakatochi, Masahiro, Scott, Robert A., Lee, Jung-Jin, Huerta-Chagoya, Alicia, Graff, Mariaelisa, Chai, Jin-Fang, Parra, Esteban J., Yao, Jie, Bielak, Lawrence F., Tabara, Yasuharu, Hai, Yang, Steinthorsdottir, Valgerdur, Cook, James P., Kals, Mart, Grarup, Niels, Schmidt, Ellen M., Pan, Ian, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloe, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Ahmad, Meraj, Noordam, Raymond, Lim, Victor J. Y., Tam, Claudia H. T., Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M., Lecoeur, Cécile, Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R., Chen, Guanjie, Jensen, Richard A., Tajuddin, Salman, Kabagambe, Edmond K., An, Ping, Xiang, Anny H., Choi, Hyeok Sun, Cade, Brian E., Tan, Jingyi, Flanagan, Jack, Abaitua, Fernando, Adair, Linda S., Adeyemo, Adebowale, Aguilar-Salinas, Carlos A., Akiyama, Masato, Anand, Sonia S., Bertoni, Alain, Bian, Zheng, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A., Brummett, Chad M., Buchanan, Thomas A., Canouil, Mickaël, Chan, Juliana C. N., Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Cushman, Mary, Das, Swapan K., de Silva, H. Janaka, Dedoussis, George, Dimitrov, Latchezar, Doumatey, Ayo P., Du, Shufa, Duan, Qing, Eckardt, Kai-Uwe, Emery, Leslie S., Evans, Daniel S., Evans, Michele K., Fischer, Krista, Floyd, James S., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Frayling, Timothy M., Freedman, Barry I., Fuchsberger, Christian, Genter, Pauline, Gerstein, Hertzel C., Giedraitis, Vilmantas, González-Villalpando, Clicerio, González-Villalpando, Maria Elena, Goodarzi, Mark O., Gordon-Larsen, Penny, Gorkin, David, Gross, Myron, Guo, Yu, Hackinger, Sophie, Han, Sohee, Hattersley, Andrew T., Herder, Christian, Howard, Annie-Green, Hsueh, Willa, Huang, Mengna, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Ikram, Mohammad Arfan, Ingelsson, Martin, Islam, Md Tariqul, Isono, Masato, Jang, Hye-Mi, Jasmine, Farzana, Jiang, Guozhi, Jonas, Jost B., Jørgensen, Marit E., Jørgensen, Torben, Kamatani, Yoichiro, Kandeel, Fouad R., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kaur, Varinderpal, Kawaguchi, Takahisa, Keaton, Jacob M., Kho, Abel N., Khor, Chiea-Chuen, Kibriya, Muhammad G., Kim, Duk-Hwan, Kohara, Katsuhiko, Kriebel, Jennifer, Kronenberg, Florian, Kuusisto, Johanna, Läll, Kristi, Lange, Leslie A., Lee, Myung-Shik, Lee, Nanette R., Leong, Aaron, Li, Liming, Li, Yun, Li-Gao, Ruifang, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Locke, Adam E., Louie, Tin, Luan, Jian’an, Luk, Andrea O., Luo, Xi, Lv, Jun, Lyssenko, Valeriya, Mamakou, Vasiliki, Mani, K. Radha, Meitinger, Thomas, Metspalu, Andres, Morris, Andrew D., Nadkarni, Girish N., Nadler, Jerry L., Nalls, Michael A., Nayak, Uma, Nongmaithem, Suraj S., Ntalla, Ioanna, Okada, Yukinori, Orozco, Lorena, Patel, Sanjay R., Pereira, Mark A., Peters, Annette, Pirie, Fraser J., Porneala, Bianca, Prasad, Gauri, Preissl, Sebastian, Rasmussen-Torvik, Laura J., Reiner, Alexander P., Roden, Michael, Rohde, Rebecca, Roll, Kathryn, Sabanayagam, Charumathi, Sander, Maike, Sandow, Kevin, Sattar, Naveed, Schönherr, Sebastian, Schurmann, Claudia, Shahriar, Mohammad, Shi, Jinxiu, Shin, Dong Mun, Shriner, Daniel, Smith, Jennifer A., So, Wing Yee, Stančáková, Alena, Stilp, Adrienne M., Strauch, Konstantin, Suzuki, Ken, Takahashi, Atsushi, Taylor, Kent D., Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tomlinson, Brian, Torres, Jason M., Tsai, Fuu-Jen, Tuomilehto, Jaakko, Tusie-Luna, Teresa, Udler, Miriam S., Valladares-Salgado, Adan, van Dam, Rob M., van Klinken, Jan B., Varma, Rohit, Vujkovic, Marijana, Wacher-Rodarte, Niels, Wheeler, Eleanor, Whitsel, Eric A., Wickremasinghe, Ananda R., van Dijk, Ko Willems, Witte, Daniel R., Yajnik, Chittaranjan S., Yamamoto, Ken, Yamauchi, Toshimasa, Yengo, Loïc, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Yusuf, Salim, Zhang, Liang, Zheng, Wei, Raffel, Leslie J., Igase, Michiya, Ipp, Eli, Redline, Susan, Cho, Yoon Shin, Lind, Lars, Province, Michael A., Hanis, Craig L., Peyser, Patricia A., Ingelsson, Erik, Zonderman, Alan B., Psaty, Bruce M., Wang, Ya-Xing, Rotimi, Charles N., Becker, Diane M., Matsuda, Fumihiko, Liu, Yongmei, Zeggini, Eleftheria, Yokota, Mitsuhiro, Rich, Stephen S., Kooperberg, Charles, Pankow, James S., Engert, James C., Chen, Yii-Der Ida, Froguel, Philippe, Wilson, James G., Sheu, Wayne H. H., Kardia, Sharon L. R., Wu, Jer-Yuarn, Hayes, M. Geoffrey, Ma, Ronald C. W., Wong, Tien-Yin, Groop, Leif, Mook-Kanamori, Dennis O., Chandak, Giriraj R., Collins, Francis S., Bharadwaj, Dwaipayan, Paré, Guillaume, Sale, Michèle M., Ahsan, Habibul, Motala, Ayesha A., Shu, Xiao-Ou, Park, Kyong-Soo, Jukema, J. Wouter, Cruz, Miguel, McKean-Cowdin, Roberta, Grallert, Harald, Cheng, Ching-Yu, Bottinger, Erwin P., Dehghan, Abbas, Tai, E-Shyong, Dupuis, Josée, Kato, Norihiro, Laakso, Markku, Köttgen, Anna, Koh, Woon-Puay, Palmer, Colin N. A., Liu, Simin, Abecasis, Goncalo, Kooner, Jaspal S., Loos, Ruth J. F., North, Kari E., Haiman, Christopher A., Florez, Jose C., Saleheen, Danish, Hansen, Torben, Pedersen, Oluf, Mägi, Reedik, Langenberg, Claudia, Wareham, Nicholas J., Maeda, Shiro, Kadowaki, Takashi, Lee, Juyoung, Millwood, Iona Y., Walters, Robin G., Stefansson, Kari, Myers, Simon R., Ferrer, Jorge, Gaulton, Kyle J., Meigs, James B., Mohlke, Karen L., Gloyn, Anna L., Bowden, Donald W., Below, Jennifer E., Chambers, John C., Sim, Xueling, Boehnke, Michael, Rotter, Jerome I., McCarthy, Mark I., and Morris, Andrew P.
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- 2022
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14. Long-term effects of intensive multifactorial treatment on aortic stiffness and central hemodynamics after 13 years with screen-detected type 2 diabetes: the ADDITION-Denmark trial
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Bjerg, Lasse, Laugesen, Esben, Andersen, Signe Toft, Rosborg, Jonas Frey, Charles, Morten, Vistisen, Dorte, and Witte, Daniel R.
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- 2022
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15. A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes
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van Zuydam, Natalie R, Ahlqvist, Emma, Sandholm, Niina, Deshmukh, Harshal, Rayner, N William, Abdalla, Moustafa, Ladenvall, Claes, Ziemek, Daniel, Fauman, Eric, Robertson, Neil R, McKeigue, Paul M, Valo, Erkka, Forsblom, Carol, Harjutsalo, Valma, Perna, Annalisa, Rurali, Erica, Marcovecchio, M Loredana, Igo, Robert P, Salem, Rany M, Perico, Norberto, Lajer, Maria, Käräjämäki, Annemari, Imamura, Minako, Kubo, Michiaki, Takahashi, Atsushi, Sim, Xueling, Liu, Jianjun, van Dam, Rob M, Jiang, Guozhi, Tam, Claudia HT, Luk, Andrea OY, Lee, Heung Man, Lim, Cadmon KP, Szeto, Cheuk Chun, So, Wing Yee, Chan, Juliana CN, Ang, Su Fen, Dorajoo, Rajkumar, Wang, Ling, Clara, Tan Si Hua, McKnight, Amy-Jayne, Duffy, Seamus, Pezzolesi, Marcus G, Marre, Michel, Gyorgy, Beata, Hadjadj, Samy, Hiraki, Linda T, Ahluwalia, Tarunveer S, Almgren, Peter, Schulz, Christina-Alexandra, Orho-Melander, Marju, Linneberg, Allan, Christensen, Cramer, Witte, Daniel R, Grarup, Niels, Brandslund, Ivan, Melander, Olle, Paterson, Andrew D, Tregouet, David, Maxwell, Alexander P, Lim, Su Chi, Ma, Ronald CW, Tai, E Shyong, Maeda, Shiro, Lyssenko, Valeriya, Tuomi, Tiinamaija, Krolewski, Andrzej S, Rich, Stephen S, Hirschhorn, Joel N, Florez, Jose C, Dunger, David, Pedersen, Oluf, Hansen, Torben, Rossing, Peter, Remuzzi, Giuseppe, Brosnan, Mary Julia, Palmer, Colin NA, Groop, Per-Henrik, Colhoun, Helen M, Groop, Leif C, McCarthy, Mark I, Koivula, S, Uggeldahl, T, Forslund, T, Halonen, A, Koistinen, A, Koskiaho, P, Laukkanen, M, Saltevo, J, Tiihonen, M, Forsen, M, Granlund, H, Jonsson, A-C, Nyroos, B, Kinnunen, P, Orvola, A, Salonen, T, Vähänen, A, Paldanius, Kotka R, and Riihelä, M
- Subjects
Diabetes ,Genetics ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Good Health and Well Being ,Adult ,Aged ,Aged ,80 and over ,Case-Control Studies ,Diabetes Mellitus ,Type 2 ,Diabetic Nephropathies ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Kidney Failure ,Chronic ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Renal Insufficiency ,Chronic ,Finnish Diabetic Nephropathy Study ,Hong Kong Diabetes Registry Theme-based Research Scheme Project Group ,Warren 3 and Genetics of Kidneys in Diabetes (GoKinD) Study Group ,GENIE (GEnetics of Nephropathy an International Effort) Consortium ,Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group ,SUrrogate markers for Micro- and Macrovascular hard endpoints for Innovative diabetes Tools (SUMMIT) Consortium ,Medical and Health Sciences ,Endocrinology & Metabolism - Abstract
Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
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- 2018
16. Longitudinal Change in Serum Neurofilament Light Chain in Type 2 Diabetes and Early Diabetic Polyneuropathy: ADDITION-Denmark
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Määttä, Laura L., primary, Andersen, Signe T., additional, Parkner, Tina, additional, Hviid, Claus V.B., additional, Bjerg, Lasse, additional, Kural, Mustafa A., additional, Charles, Morten, additional, Søndergaard, Esben, additional, Kuhle, Jens, additional, Tankisi, Hatice, additional, Witte, Daniel R., additional, and Jensen, Troels S., additional
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- 2024
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17. Use of medication in pregnancy on the rise: Study on 1.4 million Danish pregnancies from 1998 to 2018
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Thunbo, Mette Østergaard, primary, Vendelbo, Julie Hauer, additional, Witte, Daniel R., additional, Larsen, Agnete, additional, and Pedersen, Lars Henning, additional
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- 2024
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18. Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test
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Jonsson, Anna, Stinson, Sara E., Torekov, Signe S., Clausen, Tine D., Færch, Kristine, Kelstrup, Louise, Grarup, Niels, Mathiesen, Elisabeth R., Damm, Peter, Witte, Daniel R., Jørgensen, Marit E., Pedersen, Oluf, Holst, Jens Juul, and Hansen, Torben
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- 2021
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19. Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial
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Griffin, Simon J, Rutten, Guy E H M, Khunti, Kamlesh, Witte, Daniel R, Lauritzen, Torsten, Sharp, Stephen J, Dalsgaard, Else-Marie, Davies, Melanie J, Irving, Greg J, Vos, Rimke C, Webb, David R, Wareham, Nicholas J, and Sandbæk, Annelli
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- 2019
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20. Effect of familial diabetes status and age at diagnosis on type 2 diabetes risk: a nation-wide register-based study from Denmark
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Silverman-Retana, Omar, Hulman, Adam, Nielsen, Jannie, Ekstrøm, Claus T., Carstensen, Bendix, Simmons, Rebecca K., Bjerg, Lasse, Johnston, Luke W., and Witte, Daniel R.
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- 2020
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21. Large Language Models for Epidemiological Research via Automated Machine Learning: Case Study Using Data From the British National Child Development Study
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Wibaek, Rasmus, primary, Andersen, Gregers Stig, additional, Dahm, Christina C, additional, Witte, Daniel R, additional, and Hulman, Adam, additional
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- 2023
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22. National study of the prevalence of gestational diabetes mellitus among Danish women from 2004 to 2012
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JEPPESEN, CHARLOTTE, MAINDAL, HELLE T., KRISTENSEN, JETTE K., OVESEN, PER G., and WITTE, DANIEL R.
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- 2017
23. Prevalence and geographical distribution of insulin pump therapy in the Central Denmark Region and its association with metabolic parameters
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Kampmann, Ulla, Madsen, Lene Ring, Bjerg, Lasse, Witte, Daniel R., Hasselstrøm, Kjeld, Østergård, Torben, Alstrup, Kirsten, Møller, Marianne Kleis, Dylmer, Dorrit, and Hansen, Klavs Würgler
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- 2018
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24. Reversion from prediabetes to normoglycaemia and risk of cardiovascular disease and mortality: the Whitehall II cohort study
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Vistisen, Dorte, Kivimäki, Mika, Perreault, Leigh, Hulman, Adam, Witte, Daniel R., Brunner, Eric J., Tabák, Adam, Jørgensen, Marit E., and Færch, Kristine
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- 2019
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25. Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes
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Miguel-Escalada, Irene, Bonàs-Guarch, Silvia, Cebola, Inês, Ponsa-Cobas, Joan, Mendieta-Esteban, Julen, Atla, Goutham, Javierre, Biola M., Rolando, Delphine M. Y., Farabella, Irene, Morgan, Claire C., García-Hurtado, Javier, Beucher, Anthony, Morán, Ignasi, Pasquali, Lorenzo, Ramos-Rodríguez, Mireia, Appel, Emil V. R., Linneberg, Allan, Gjesing, Anette P., Witte, Daniel R., Pedersen, Oluf, Grarup, Niels, Ravassard, Philippe, Torrents, David, Mercader, Josep M., Piemonti, Lorenzo, Berney, Thierry, de Koning, Eelco J. P., Kerr-Conte, Julie, Pattou, François, Fedko, Iryna O., Groop, Leif, Prokopenko, Inga, Hansen, Torben, Marti-Renom, Marc A., Fraser, Peter, and Ferrer, Jorge
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- 2019
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26. Effect of duration and burden of microvascular complications on mortality rate in type 1 diabetes: an observational clinical cohort study
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Bjerg, Lasse, Hulman, Adam, Carstensen, Bendix, Charles, Morten, Witte, Daniel R., and Jørgensen, Marit E.
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- 2019
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27. No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels
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Scott, Robert A, Chu, Audrey Y, Grarup, Niels, Manning, Alisa K, Hivert, Marie-France, Shungin, Dmitry, Tönjes, Anke, Yesupriya, Ajay, Barnes, Daniel, Bouatia-Naji, Nabila, Glazer, Nicole L, Jackson, Anne U, Kutalik, Zoltán, Lagou, Vasiliki, Marek, Diana, Rasmussen-Torvik, Laura J, Stringham, Heather M, Tanaka, Toshiko, Aadahl, Mette, Arking, Dan E, Bergmann, Sven, Boerwinkle, Eric, Bonnycastle, Lori L, Bornstein, Stefan R, Brunner, Eric, Bumpstead, Suzannah J, Brage, Soren, Carlson, Olga D, Chen, Han, Chen, Yii-Der Ida, Chines, Peter S, Collins, Francis S, Couper, David J, Dennison, Elaine M, Dowling, Nicole F, Egan, Josephine S, Ekelund, Ulf, Erdos, Michael R, Forouhi, Nita G, Fox, Caroline S, Goodarzi, Mark O, Grässler, Jürgen, Gustafsson, Stefan, Hallmans, Göran, Hansen, Torben, Hingorani, Aroon, Holloway, John W, Hu, Frank B, Isomaa, Bo, Jameson, Karen A, Johansson, Ingegerd, Jonsson, Anna, Jørgensen, Torben, Kivimaki, Mika, Kovacs, Peter, Kumari, Meena, Kuusisto, Johanna, Laakso, Markku, Lecoeur, Cécile, Lévy-Marchal, Claire, Li, Guo, Loos, Ruth JF, Lyssenko, Valeri, Marmot, Michael, Marques-Vidal, Pedro, Morken, Mario A, Müller, Gabriele, North, Kari E, Pankow, James S, Payne, Felicity, Prokopenko, Inga, Psaty, Bruce M, Renström, Frida, Rice, Ken, Rotter, Jerome I, Rybin, Denis, Sandholt, Camilla H, Sayer, Avan A, Shrader, Peter, Schwarz, Peter EH, Siscovick, David S, Stančáková, Alena, Stumvoll, Michael, Teslovich, Tanya M, Waeber, Gérard, Williams, Gordon H, Witte, Daniel R, Wood, Andrew R, Xie, Weijia, Boehnke, Michael, Cooper, Cyrus, Ferrucci, Luigi, Froguel, Philippe, Groop, Leif, Kao, WH Linda, Vollenweider, Peter, Walker, Mark, Watanabe, Richard M, Pedersen, Oluf, and Meigs, James B
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Biomedical and Clinical Sciences ,Clinical Research ,Genetics ,Diabetes ,Prevention ,Obesity ,Nutrition ,2.1 Biological and endogenous factors ,Aetiology ,2.3 Psychological ,social and economic factors ,Metabolic and endocrine ,Blood Glucose ,Body Mass Index ,Epigenesis ,Genetic ,Gene Expression Regulation ,Genotype ,Humans ,Life Style ,Motor Activity ,Polymorphism ,Single Nucleotide ,Medical and Health Sciences ,Endocrinology & Metabolism ,Biomedical and clinical sciences - Abstract
Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
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- 2012
28. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.
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Lohmueller, Kirk E, Albrechtsen, Anders, Li, Yingrui, Kim, Su Yeon, Korneliussen, Thorfinn, Vinckenbosch, Nicolas, Tian, Geng, Huerta-Sanchez, Emilia, Feder, Alison F, Grarup, Niels, Jørgensen, Torben, Jiang, Tao, Witte, Daniel R, Sandbæk, Annelli, Hellmann, Ines, Lauritzen, Torsten, Hansen, Torben, Pedersen, Oluf, Wang, Jun, and Nielsen, Rasmus
- Subjects
Animals ,Humans ,Pan troglodytes ,Evolution ,Molecular ,Recombination ,Genetic ,Gene Frequency ,Genetic Drift ,Mutation ,Genome ,Human ,Models ,Genetic ,Population ,Genetic Variation ,Selection ,Genetic ,Human Genome ,Biotechnology ,Genetics ,Generic health relevance ,Developmental Biology - Abstract
A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.
- Published
- 2011
29. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps
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Mahajan, Anubha, Taliun, Daniel, Thurner, Matthias, Robertson, Neil R., Torres, Jason M., Rayner, N. William, Payne, Anthony J., Steinthorsdottir, Valgerdur, Scott, Robert A., Grarup, Niels, Cook, James P., Schmidt, Ellen M., Wuttke, Matthias, Sarnowski, Chloé, Mägi, Reedik, Nano, Jana, Gieger, Christian, Trompet, Stella, Lecoeur, Cécile, Preuss, Michael H., Prins, Bram Peter, Guo, Xiuqing, Bielak, Lawrence F., Below, Jennifer E., Bowden, Donald W., Chambers, John Campbell, Kim, Young Jin, Ng, Maggie C. Y., Petty, Lauren E., Sim, Xueling, Zhang, Weihua, Bennett, Amanda J., Bork-Jensen, Jette, Brummett, Chad M., Canouil, Mickaël, Ec kardt, Kai-Uwe, Fischer, Krista, Kardia, Sharon L. R., Kronenberg, Florian, Läll, Kristi, Liu, Ching-Ti, Locke, Adam E., Luan, Jian’an, Ntalla, Ioanna, Nylander, Vibe, Schönherr, Sebastian, Schurmann, Claudia, Yengo, Loïc, Bottinger, Erwin P., Brandslund, Ivan, Christensen, Cramer, Dedoussis, George, Florez, Jose C., Ford, Ian, Franco, Oscar H., Frayling, Timothy M., Giedraitis, Vilmantas, Hackinger, Sophie, Hattersley, Andrew T., Herder, Christian, Ikram, M. Arfan, Ingelsson, Martin, Jørgensen, Marit E., Jørgensen, Torben, Kriebel, Jennifer, Kuusisto, Johanna, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Lyssenko, Valeriya, Mamakou, Vasiliki, Meitinger, Thomas, Mohlke, Karen L., Morris, Andrew D., Nadkarni, Girish, Pankow, James S., Peters, Annette, Sattar, Naveed, Stančáková, Alena, Strauch, Konstantin, Taylor, Kent D., Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tuomilehto, Jaakko, Witte, Daniel R., Dupuis, Josée, Peyser, Patricia A., Zeggini, Eleftheria, Loos, Ruth J. F., Froguel, Philippe, Ingelsson, Erik, Lind, Lars, Groop, Leif, Laakso, Markku, Collins, Francis S., Jukema, J. Wouter, Palmer, Colin N. A., Grallert, Harald, Metspalu, Andres, Dehghan, Abbas, Köttgen, Anna, Abecasis, Goncalo R., Meigs, James B., Rotter, Jerome I., Marchini, Jonathan, Pedersen, Oluf, Hansen, Torben, Langenberg, Claudia, Wareham, Nicholas J., Stefansson, Kari, Gloyn, Anna L., Morris, Andrew P., Boehnke, Michael, and McCarthy, Mark I.
- Published
- 2018
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30. Spousal cardiometabolic risk factors and incidence of type 2 diabetes: a prospective analysis from the English Longitudinal Study of Ageing
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Nielsen, Jannie, Hulman, Adam, and Witte, Daniel R.
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- 2018
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31. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
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Mahajan, Anubha, Wessel, Jennifer, Willems, Sara M., Zhao, Wei, Robertson, Neil R., Chu, Audrey Y., Gan, Wei, Kitajima, Hidetoshi, Taliun, Daniel, Rayner, N. William, Guo, Xiuqing, Lu, Yingchang, Li, Man, Jensen, Richard A., Hu, Yao, Huo, Shaofeng, Lohman, Kurt K., Zhang, Weihua, Cook, James P., Prins, Bram Peter, Flannick, Jason, Grarup, Niels, Trubetskoy, Vassily Vladimirovich, Kravic, Jasmina, Kim, Young Jin, Rybin, Denis V., Yaghootkar, Hanieh, Müller-Nurasyid, Martina, Meidtner, Karina, Li-Gao, Ruifang, Varga, Tibor V., Marten, Jonathan, Li, Jin, Smith, Albert Vernon, An, Ping, Ligthart, Symen, Gustafsson, Stefan, Malerba, Giovanni, Demirkan, Ayse, Tajes, Juan Fernandez, Steinthorsdottir, Valgerdur, Wuttke, Matthias, Lecoeur, Cécile, Preuss, Michael, Bielak, Lawrence F., Graff, Marielisa, Highland, Heather M., Justice, Anne E., Liu, Dajiang J., Marouli, Eirini, Peloso, Gina Marie, Warren, Helen R., Afaq, Saima, Afzal, Shoaib, Ahlqvist, Emma, Almgren, Peter, Amin, Najaf, Bang, Lia B., Bertoni, Alain G., Bombieri, Cristina, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A., Burtt, Noël P., Canouil, Mickaël, Chen, Yii-Der Ida, Cho, Yoon Shin, Christensen, Cramer, Eastwood, Sophie V., Eckardt, Kai-Uwe, Fischer, Krista, Gambaro, Giovanni, Giedraitis, Vilmantas, Grove, Megan L., de Haan, Hugoline G., Hackinger, Sophie, Hai, Yang, Han, Sohee, Tybjærg-Hansen, Anne, Hivert, Marie-France, Isomaa, Bo, Jäger, Susanne, Jørgensen, Marit E., Jørgensen, Torben, Käräjämäki, Annemari, Kim, Bong-Jo, Kim, Sung Soo, Koistinen, Heikki A., Kovacs, Peter, Kriebel, Jennifer, Kronenberg, Florian, Läll, Kristi, Lange, Leslie A., Lee, Jung-Jin, Lehne, Benjamin, Li, Huaixing, Lin, Keng-Hung, Linneberg, Allan, Liu, Ching-Ti, Liu, Jun, Loh, Marie, Mägi, Reedik, Mamakou, Vasiliki, McKean-Cowdin, Roberta, Nadkarni, Girish, Neville, Matt, Nielsen, Sune F., Ntalla, Ioanna, Peyser, Patricia A., Rathmann, Wolfgang, Rice, Kenneth, Rich, Stephen S., Rode, Line, Rolandsson, Olov, Schönherr, Sebastian, Selvin, Elizabeth, Small, Kerrin S., Stančáková, Alena, Surendran, Praveen, Taylor, Kent D., Teslovich, Tanya M., Thorand, Barbara, Thorleifsson, Gudmar, Tin, Adrienne, Tönjes, Anke, Varbo, Anette, Witte, Daniel R., Wood, Andrew R., Yajnik, Pranav, Yao, Jie, Yengo, Loïc, Young, Robin, Amouyel, Philippe, Boeing, Heiner, Boerwinkle, Eric, Bottinger, Erwin P., Chowdhury, Rajiv, Collins, Francis S., Dedoussis, George, Dehghan, Abbas, Deloukas, Panos, Ferrario, Marco M., Ferrières, Jean, Florez, Jose C., Frossard, Philippe, Gudnason, Vilmundur, Harris, Tamara B., Heckbert, Susan R., Howson, Joanna M. M., Ingelsson, Martin, Kathiresan, Sekar, Kee, Frank, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J., Lindgren, Cecilia M., Männistö, Satu, Meitinger, Thomas, Melander, Olle, Mohlke, Karen L., Moitry, Marie, Morris, Andrew D., Murray, Alison D., de Mutsert, Renée, Orho-Melander, Marju, Owen, Katharine R., Perola, Markus, Peters, Annette, Province, Michael A., Rasheed, Asif, Ridker, Paul M., Rivadineira, Fernando, Rosendaal, Frits R., Rosengren, Anders H., Salomaa, Veikko, Sheu, Wayne H.-H., Sladek, Rob, Smith, Blair H., Strauch, Konstantin, Uitterlinden, André G., Varma, Rohit, Willer, Cristen J., Blüher, Matthias, Butterworth, Adam S., Chambers, John Campbell, Chasman, Daniel I., Danesh, John, van Duijn, Cornelia, Dupuis, Josée, Franco, Oscar H., Franks, Paul W., Froguel, Philippe, Grallert, Harald, Groop, Leif, Han, Bok-Ghee, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Ingelsson, Erik, Kardia, Sharon L. R., Karpe, Fredrik, Kooner, Jaspal Singh, Köttgen, Anna, Kuulasmaa, Kari, Laakso, Markku, Lin, Xu, Lind, Lars, Liu, Yongmei, Loos, Ruth J. F., Marchini, Jonathan, Metspalu, Andres, Mook-Kanamori, Dennis, Nordestgaard, Børge G., Palmer, Colin N. A., Pankow, James S., Pedersen, Oluf, Psaty, Bruce M., Rauramaa, Rainer, Sattar, Naveed, Schulze, Matthias B., Soranzo, Nicole, Spector, Timothy D., Stefansson, Kari, Stumvoll, Michael, Thorsteinsdottir, Unnur, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Wareham, Nicholas J., Wilson, James G., Zeggini, Eleftheria, Scott, Robert A., Barroso, Inês, Frayling, Timothy M., Goodarzi, Mark O., Meigs, James B., Boehnke, Michael, Saleheen, Danish, Morris, Andrew P., Rotter, Jerome I., and McCarthy, Mark I.
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- 2018
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32. Evidence of a liver–alpha cell axis in humans: hepatic insulin resistance attenuates relationship between fasting plasma glucagon and glucagonotropic amino acids
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Wewer Albrechtsen, Nicolai J., Færch, Kristine, Jensen, Troels M., Witte, Daniel R., Pedersen, Jens, Mahendran, Yuvaraj, Jonsson, Anna E., Galsgaard, Katrine D., Winther-Sørensen, Marie, Torekov, Signe S., Lauritzen, Torsten, Pedersen, Oluf, Knop, Filip K., Hansen, Torben, Jørgensen, Marit E., Vistisen, Dorte, and Holst, Jens J.
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- 2018
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33. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
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Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D’Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian’an, Lubitz, Steven A., Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O’Connel, Jeffrey R., O’Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.-H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.
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- 2018
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34. Glucose patterns during an oral glucose tolerance test and associations with future diabetes, cardiovascular disease and all-cause mortality rate
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Hulman, Adam, Vistisen, Dorte, Glümer, Charlotte, Bergman, Michael, Witte, Daniel R., and Færch, Kristine
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- 2018
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35. Correction to: Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the ADDITION-PRO cohort
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Deichgræber, Pia, Witte, Daniel R., Møller, Holger J., Skriver, Mette V., Richelsen, Bjørn, Jørgensen, Marit E., Johansen, Nanna B., and Sandbæk, Annelli
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- 2017
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36. Autonomic dysfunction is associated with the development of arterial stiffness:the Whitehall II cohort
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Schaarup, Jonas R., Christensen, Martin S., Hulman, Adam, Hansen, Christian S., Vistisen, Dorte, Tabak, Adam G., Witte, Daniel R., Bjerg, Lasse, Schaarup, Jonas R., Christensen, Martin S., Hulman, Adam, Hansen, Christian S., Vistisen, Dorte, Tabak, Adam G., Witte, Daniel R., and Bjerg, Lasse
- Abstract
This study aims to examine the association between baseline level and change of autonomic nervous function with subsequent development of arterial stiffness. Autonomic nervous function was assessed in 4901 participants of the Whitehall II occupational cohort by heart rate variability (HRV) indices and resting heart rate (rHR) three times between 1997 and 2009, while arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) measured twice between 2007 and 2013. First, individual HRV/rHR levels and annual changes were estimated. Then, we modelled the development of PWV by HRV/rHR using linear mixed effect models. First, we adjusted for sex and ethnicity (model 1), and then for socioeconomic and lifestyle factors, various clinical measurements, and medications (model 2). A decrease in HRV and unchanged rHR was associated with subsequent higher levels of PWV, but the effect of a change in HRV was less pronounced at higher ages. A typical individual aged 65 years with a SDNN level of 30 ms and a 2% annual decrease in SDNN had 1.32 (0.95; 1.69) higher PWV compared to one with the same age and SDNN level but with a 1% annual decrease in SDNN. Further adjustment had no major effect on the results. People who experience a steeper decline in autonomic nervous function have higher levels of arterial stiffness. The association was stronger in younger people., This study aims to examine the association between baseline level and change of autonomic nervous function with subsequent development of arterial stiffness. Autonomic nervous function was assessed in 4901 participants of the Whitehall II occupational cohort by heart rate variability (HRV) indices and resting heart rate (rHR) three times between 1997 and 2009, while arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) measured twice between 2007 and 2013. First, individual HRV/rHR levels and annual changes were estimated. Then, we modelled the development of PWV by HRV/rHR using linear mixed effect models. First, we adjusted for sex and ethnicity (model 1), and then for socioeconomic and lifestyle factors, various clinical measurements, and medications (model 2). A decrease in HRV and unchanged rHR was associated with subsequent higher levels of PWV, but the effect of a change in HRV was less pronounced at higher ages. A typical individual aged 65 years with a SDNN level of 30 ms and a 2% annual decrease in SDNN had 1.32 (0.95; 1.69) higher PWV compared to one with the same age and SDNN level but with a 1% annual decrease in SDNN. Further adjustment had no major effect on the results. People who experience a steeper decline in autonomic nervous function have higher levels of arterial stiffness. The association was stronger in younger people.
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- 2023
37. The association between sleep duration and detailed measures of obesity:A cross sectional analysis in the ADDITION-PRO study
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Andersen, Mie M., Laurberg, Tinne, Bjerregaard, Anne Louise, Sandbæk, Annelli, Brage, Søren, Vistisen, Dorte, Quist, Jonas S., Bruun, Jens M., Witte, Daniel R., Andersen, Mie M., Laurberg, Tinne, Bjerregaard, Anne Louise, Sandbæk, Annelli, Brage, Søren, Vistisen, Dorte, Quist, Jonas S., Bruun, Jens M., and Witte, Daniel R.
- Abstract
Background: Sleep duration is associated with BMI and waist circumference. However, less is known about whether sleep duration affects different measurements of obesity differently. Objective: To investigate the association between sleep duration and different measures of obesity. Methods: In this cross-sectional analysis 1309, Danish, older adults (55% men) completed at least 3 days of wearing a combined accelerometer and heart rate-monitor for assessing sleep duration (hours/night) within self-reported usual bedtime. Participants underwent anthropometry and ultrasonography to assess BMI, waist circumference, visceral fat, subcutaneous fat, and fat percentage. Linear regression analyses examined the associations between sleep duration and obesity-related outcomes. Results: Sleep duration was inversely associated with all obesity-related outcomes, except visceral-/subcutaneous-fat-ratio. After multivariate adjustment the magnitude of associations became stronger and statistically significant for all outcomes except visceral-/subcutaneous-fat-ratio, and subcutaneous fat in women. The associations with BMI and waist circumference demonstrated the strongest associations, when comparing standardized regression coefficients. Conclusions: Shorter sleep duration were associated with higher obesity across all outcomes except visceral-/subcutaneous-fat-ratio. No specifically salient associations with local or central obesity were observed. Results suggest that poor sleep duration and obesity correlate, however, further research is needed to conclude on beneficial effects of sleep duration regarding health and weight loss.
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- 2023
38. Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications
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Suzuki, Ken, Hatzikotoulas, Konstantinos, Southam, Lorraine, Taylor, Henry J., Yin, Xianyong, Lorenz, Kim M., Mandla, Ravi, Huerta-Chagoya, Alicia, Rayner, Nigel W., Bocher, Ozvan, Ana Luiza de, S. V. Arruda, Sonehara, Kyuto, Namba, Shinichi, Lee, Simon S. K., Preuss, Michael H., Petty, Lauren E., Schroeder, Philip, Vanderwerff, Brett, Kals, Mart, Bragg, Fiona, Lin, Kuang, Guo, Xiuqing, Zhang, Weihua, Yao, Jie, Kim, Young Jin, Graff, Mariaelisa, Takeuchi, Fumihiko, Nano, Jana, Lamri, Amel, Nakatochi, Masahiro, Moon, Sanghoon, Scott, Robert A., Cook, James P., Lee, Jung-Jin, Pan, Ian, Taliun, Daniel, Parra, Esteban J., Chai, Jin-Fang, Bielak, Lawrence F., Tabara, Yasuharu, Hai, Yang, Thorleifsson, Gudmar, Grarup, Niels, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloé, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Kwak, Soo-Heon, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Nongmaithem, Suraj S., Noordam, Raymond, Lim, Victor J. Y., Tam, Claudia H. T., Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M., Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R., Chen, Guanjie, Brody, Jennifer A., Kabagambe, Edmond, An, Ping, Xiang, Anny H., Choi, Hyeok Sun, Cade, Brian E., Tan, Jingyi, Alaine Broadaway, K., Williamson, Alice, Kamali, Zoha, Cui, Jinrui, Adair, Linda S., Adeyemo, Adebowale, Aguilar-Salinas, Carlos A., Ahluwalia, Tarunveer S., Anand, Sonia S., Bertoni, Alain, Bork-Jensen, Jette, Brandslund, Ivan, Buchanan, Thomas A., Burant, Charles F., Butterworth, Adam S., Canouil, Mickaël, Chan, Juliana C. N., Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Cushman, Mary, Danesh, John, Das, Swapan K., Janaka de Silva, H., Dedoussis, George, Dimitrov, Latchezar, Doumatey, Ayo P., Du, Shufa, Duan, Qing, Eckardt, Kai-Uwe, Emery, Leslie S., Evans, Daniel S., Evans, Michele K., Fischer, Krista, Floyd, James S., Ford, Ian, Franco, Oscar H., Frayling, Timothy M., Freedman, Barry I., Genter, Pauline, Gerstein, Hertzel C., Giedraitis, Vilmantas, González-Villalpando, Clicerio, González-Villalpando, Maria Elena, Gordon-Larsen, Penny, Gross, Myron, Guare, Lindsay A., Hackinger, Sophie, Han, Sohee, Hattersley, Andrew T., Herder, Christian, Horikoshi, Momoko, Howard, Annie-Green, Hsueh, Willa, Huang, Mengna, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Ikram, Mohammad Arfan, Ingelsson, Martin, Islam, Md. Tariqul, Isono, Masato, Jang, Hye-Mi, Jasmine, Farzana, Jiang, Guozhi, Jonas, Jost B., Jørgensen, Torben, Kandeel, Fouad R., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kaur, Varinderpal, Kawaguchi, Takahisa, Keaton, Jacob M., Kho, Abel N., Khor, Chiea-Chuen, Kibriya, Muhammad G., Kim, Duk-Hwan, Kronenberg, Florian, Kuusisto, Johanna, Läll, Kristi, Lange, Leslie A., Lee, Kyung Min, Lee, Myung-Shik, Lee, Nanette R., Leong, Aaron, Li, Liming, Li, Yun, Li-Gao, Ruifang, Lithgart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Locke, Adam E., Louie, Tin, Luan, Jian’an, Luk, Andrea O., Luo, Xi, Lv, Jun, Lynch, Julie A., Lyssenko, Valeriya, Maeda, Shiro, Mamakou, Vasiliki, Mansuri, Sohail Rafik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Mo, Huan, Morris, Andrew D., Nadler, Jerry L., Nalls, Michael A., Nayak, Uma, Ntalla, Ioanna, Okada, Yukinori, Orozco, Lorena, Patel, Sanjay R., Patil, Snehal, Pei, Pei, Pereira, Mark A, Peters, Annette, Pirie, Fraser J., Polikowsky, Hannah G., Porneala, Bianca, Prasad, Gauri, Rasmussen-Torvik, Laura J., Reiner, Alexander P., Roden, Michael, Rohde, Rebecca, Roll, Katheryn, Sabanayagam, Charumathi, Sandow, Kevin, Sankareswaran, Alagu, Sattar, Naveed, Schönherr, Sebastian, Shahriar, Mohammad, Shen, Botong, Shi, Jinxiu, Shin, Dong Mun, Shojima, Nobuhiro, Smith, Jennifer A., So, Wing Yee, Stančáková, Alena, Steinthorsdottir, Valgerdur, Stilp, Adrienne M., Strauch, Konstantin, Taylor, Kent D., Thorand, Barbara, Thorsteinsdottir, Unnur, Tomlinson, Brian, Tran, Tam C., Tsai, Fuu-Jen, Tuomilehto, Jaakko, Tusie-Luna, Teresa, Udler, Miriam S., Valladares-Salgado, Adan, van Dam, Rob M., van Klinken, Jan B., Varma, Rohit, Wacher-Rodarte, Niels, Wheeler, Eleanor, Wickremasinghe, Ananda R., van Dijk, Ko Willems, Witte, Daniel R., Yajnik, Chittaranjan S., Yamamoto, Ken, Yamamoto, Kenichi, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Yusuf, Salim, Zawistowski, Matthew, Zhang, Liang, Zheng, Wei, Project, Biobank Japan, BioBank, Penn Medicine, Center, Regeneron Genetics, Consortium, eMERGE, Raffel, Leslie J, Igase, Michiya, Ipp, Eli, Redline, Susan, Cho, Yoon Shin, Lind, Lars, Province, Michael A., Fornage, Myriam, Hanis, Craig L., Ingelsson, Erik, Zonderman, Alan B., Psaty, Bruce M., Wang, Ya-Xing, Rotimi, Charles N., Becker, Diane M., Matsuda, Fumihiko, Liu, Yongmei, Yokota, Mitsuhiro, Kardia, Sharon L. R., Peyser, Patricia A., Pankow, James S., Engert, James C., Bonnefond, Amélie, Froguel, Philippe, Wilson, James G., Sheu, Wayne H. H., Wu, Jer-Yuarn, Geoffrey Hayes, M., Ma, Ronald C. W., Wong, Tien-Yin, Mook-Kanamori, Dennis O., Tuomi, Tiinamaija, Chandak, Giriraj R., Collins, Francis S., Bharadwaj, Dwaipayan, Paré, Guillaume, Sale, Michèle M., Ahsan, Habibul, Motala, Ayesha A., Shu, Xiao-Ou, Park, Kyong-Soo, Jukema, J Wouter, Cruz, Miguel, Chen, Yii-Der Ida, Rich, Stephen S., McKean-Cowdin, Roberta, Grallert, Harald, Cheng, Ching-Yu, Ghanbari, Mohsen, Tai, E-Shyong, Dupuis, Josee, Kato, Norihiro, Laakso, Markku, Köttgen, Anna, Koh, Woon-Puay, Bowden, Donald W., Palmer, Colin N. A., Kooner, Jaspal S., Kooperberg, Charles, Liu, Simin, North, Kari E., Saleheen, Danish, Hansen, Torben, Pedersen, Oluf, Wareham, Nicholas J., Lee, Juyoung, Kim, Bong-Jo, Millwood, Iona Y., Walters, Robin G., Stefansson, Kari, Goodarzi, Mark O., Mohlke, Karen L., Langenberg, Claudia, Haiman, Christopher A., Loos, Ruth J. F., Florez, Jose C., Rader, Daniel J., Ritchie, Marylyn D., Zöllner, Sebastian, Mägi, Reedik, Denny, Joshua C., Yamauchi, Toshimasa, Kadowaki, Takashi, Chambers, John C., Ng, Maggie C. Y., Sim, Xueling, Below, Jennifer E., Tsao, Philip S., Chang, Kyong-Mi, McCarthy, Mark I., Meigs, James B., Mahajan, Anubha, Spracklen, Cassandra N., Mercader, Josep M., Boehnke, Michael, Rotter, Jerome I., Vujkovic, Marijana, Voight, Benjamin F., Morris, Andrew P., and Zeggini, Eleftheria
- Subjects
Article - Abstract
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,289 independent association signals at genome-wide significance (P
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- 2023
39. Greater glucagon-like peptide-1 responses to oral glucose are associated with lower central and peripheral blood pressures
- Author
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Lundgren, Julie R., Færch, Kristine, Witte, Daniel R., Jonsson, Anna E., Pedersen, Oluf, Hansen, Torben, Lauritzen, Torsten, Holst, Jens J., Vistisen, Dorte, Jørgensen, Marit E., Torekov, Signe S., and Johansen, Nanna B.
- Published
- 2019
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40. The STC2 – PAPP-A – IGFBP4 – IGF1 axis and associations to mortality and CVD in T2D
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Gude, Mette Faurholdt, primary, Hjortebjerg, Rikke, additional, Bjerre, Mette, additional, Charles, Morten Haaning, additional, Witte, Daniel R, additional, Sandbæk, Annelli, additional, and Frystyk, Jan, additional
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- 2023
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41. Association of self-perceived body image with body mass index and type 2 diabetes—The ADDITION-PRO study
- Author
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Bjerggaard, Mette, Philipsen, Annelotte, Jørgensen, Marit E., Charles, Morten, Witte, Daniel R., Sandbæk, Annelli, Lauritzen, Torsten, and Færch, Kristine
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- 2015
- Full Text
- View/download PDF
42. Heterogeneous effect of gestational weight gain on birth weight: quantile regression analysis from a population-based screening
- Author
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Hulmán, Adam, Witte, Daniel R., Kerényi, Zsuzsa, Madarász, Eszter, Tänczer, Tímea, Bosnyák, Zsolt, Szabó, Eszter, Ferencz, Viktória, Péterfalvi, Andrea, Tabák, Adam G., and Nyári, Tibor A.
- Published
- 2015
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43. Effect of population screening for type 2 diabetes and cardiovascular risk factors on mortality rate and cardiovascular events: a controlled trial among 1,912,392 Danish adults
- Author
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Simmons, Rebecca K., Griffin, Simon J., Witte, Daniel R., Borch-Johnsen, Knut, Lauritzen, Torsten, and Sandbæk, Annelli
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- 2017
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44. Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study
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Hulman, Adam, Simmons, Rebecca K., Brunner, Eric J., Witte, Daniel R., Færch, Kristine, Vistisen, Dorte, Ikehara, Satoyo, Kivimaki, Mika, and Tabák, Adam G.
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- 2017
- Full Text
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45. Does training of general practitioners for intensive treatment of people with screen-detected diabetes have a spillover effect on mortality and cardiovascular morbidity in ‘at risk’ individuals with normoglycaemia? Results from the ADDITION-Denmark cluster-randomised controlled trial
- Author
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Simmons, Rebecca K., Bruun, Niels H., Witte, Daniel R., Borch-Johnsen, Knut, Jørgensen, Marit E., Sandbæk, Annelli, and Lauritzen, Torsten
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- 2017
- Full Text
- View/download PDF
46. Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels
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Mahendran, Yuvaraj, Jonsson, Anna, Have, Christian T., Allin, Kristine H., Witte, Daniel R., Jørgensen, Marit E., Grarup, Niels, Pedersen, Oluf, Kilpeläinen, Tuomas O., and Hansen, Torben
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- 2017
- Full Text
- View/download PDF
47. Effectiveness of Liraglutide and Lixisenatide in the Treatment of Type 2 Diabetes: Real-World Evidence from The Health Improvement Network (THIN) Database in the United Kingdom
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Feher, Michael, Vega-Hernandez, Gabriela, Mocevic, Emina, Buysse, Brian, Myland, Melissa, Power, Geraldine S., Nystrup Husemoen, Lise L., Kim, Joseph, and Witte, Daniel R.
- Published
- 2017
- Full Text
- View/download PDF
48. Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk
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Hulman, Adam, Simmons, Rebecca K., Vistisen, Dorte, Tabák, Adam G., Dekker, Jacqueline M., Alssema, Marjan, Rutters, Femke, Koopman, Anitra D. M., Solomon, Thomas P. J., Kirwan, John P., Hansen, Torben, Jonsson, Anna, Gjesing, Anette Prior, Eiberg, Hans, Astrup, Arne, Pedersen, Oluf, Sørensen, Thorkild I. A., Witte, Daniel R., and Færch, Kristine
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- 2017
- Full Text
- View/download PDF
49. Association of general health and lifestyle factors with the salivary microbiota – Lessons learned from the ADDITION-PRO cohort
- Author
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Poulsen, Casper Sahl, primary, Nygaard, Nikoline, additional, Constancias, Florentin, additional, Stankevic, Evelina, additional, Kern, Timo, additional, Witte, Daniel R., additional, Vistisen, Dorte, additional, Grarup, Niels, additional, Pedersen, Oluf Borbye, additional, Belstrøm, Daniel, additional, and Hansen, Torben, additional
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- 2022
- Full Text
- View/download PDF
50. Large language models for epidemiological research via automated machine learning: a case study and method comparison from the British National Child Development Study (Preprint)
- Author
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Wibaek, Rasmus, primary, Andersen, Gregers Stig, additional, Dahm, Christina C, additional, Witte, Daniel R, additional, and Hulman, Adam, additional
- Published
- 2022
- Full Text
- View/download PDF
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