50 results on '"Lee, N. R."'
Search Results
2. Appropriate non-carbapenems are not inferior to carbapenems as initial empirical therapy for bacteremia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a propensity score weighted multicenter cohort study
- Author
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Ko, J.-H., Lee, N. R., Joo, E.-J., Moon, S.-y., Choi, J.-K., Park, D. A., and Peck, K. R.
- Published
- 2017
- Full Text
- View/download PDF
3. Impact of appropriateness of empiric therapy on outcomes in community-onset bacteremia by extended-spectrum-β-lactamase producing Escherichia coli and Klebisella pneumoniae definitively treated with carbapenems
- Author
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Joo, E.-J., Park, D. A., Lee, N. R., Moon, S.-y., Choi, J.-K., Ko, J.-H., and Peck, K. R.
- Published
- 2017
- Full Text
- View/download PDF
4. Latent profiles of autism symptoms in children and adolescents with Down syndrome
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Fidler, D. J., primary, Prince, M. A., additional, Van Deusen, K., additional, Esbensen, A. J., additional, Thurman, A. J., additional, Abbeduto, L., additional, Patel, L., additional, Mervis, C., additional, Schworer, E. K., additional, Lee, N. R., additional, Edgin, J. O., additional, Hepburn, S., additional, Davis, S., additional, and Daunhauer, L. A., additional
- Published
- 2022
- Full Text
- View/download PDF
5. Confirmatory factor analysis of the BRIEF2 in a sample of youth with Down syndrome.
- Author
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Soltani, A., Schworer, E. K., Jacobson, L. A., Channell, M. M., Lee, N. R., Faught, G. G., Grzadzinski, R., Fidler, D., and Esbensen, A. J.
- Subjects
EXECUTIVE function ,DOWN syndrome ,BEHAVIORAL assessment ,BEHAVIOR ,FACTOR analysis ,RESEARCH funding ,EMOTION regulation ,PARENTS - Abstract
Background: The factor structure of the Behavior Rating Inventory of Executive Function, second edition (BRIEF2) has been widely examined in both typically developing children and specific clinical samples. Despite the frequent use of the BRIEF2 for measuring executive functioning in individuals with Down syndrome, no study has investigated the factorial validity or dimensionality of the BRIEF2 in this population. This study aimed to address this notable gap in the literature. Methods: Parents of 407 children and youth with Down syndrome aged 6–18 years completed the BRIEF2 as part of different studies led by six sites. Three competing models proposed by previous studies were analysed using Confirmatory Factor Analysis: the theoretical structure of the BRIEF2 where the scales were constrained to load on three factors labelled as Cognitive, Behavioral, and Emotional Regulation, a two‐factor correlated model with the merged Behavioral and Emotional regulation, and a single‐factor model. Results: The three‐factor model provided a better fit than the one‐ and two‐factor models, yet a large correlation was observed between Behavioural and Emotional regulation factors. The results provide meaningful explanatory value for the theoretical structure of the BRIEF2. However, the Behavioral and Emotional regulation factors might be less differentiated and the two‐factor structure of the BRIEF2 may also make theoretical and empirical sense. Conclusions: Although more studies are needed to further examine the factor structure of the BRIEF2 in youth with Down syndrome, this investigation provides preliminary support for the interpretation of the three executive function index scores provided by the BRIEF2: Cognitive, Behavioral, and Emotional Regulation. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Updated profiles of everyday executive function in youth with Down syndrome using the BRIEF‐2
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Csumitta, K. D., primary, Stephan, C. M., additional, LaQuaglia, R. I., additional, Miller, E., additional, and Lee, N. R., additional
- Published
- 2021
- Full Text
- View/download PDF
7. The trans-ancestral genomic architecture of glycemic traits
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Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), Barroso, I. (Ines), Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), and Barroso, I. (Ines)
- Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
- Published
- 2021
8. The trans-ancestral genomic architecture of glycemic traits
- Author
-
Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), Tremoli E., Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), and Tremoli E.
- Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
- Published
- 2021
9. School-age outcomes of newborns treated for persistent pulmonary hypertension
- Author
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Rosenberg, A A, Lee, N R, Vaver, K N, Werner, D, Fashaw, L, Hale, K, and Waas, N
- Published
- 2010
- Full Text
- View/download PDF
10. A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome
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Lenroot, R. K., Blumenthal, J. D., Wallace, G. L., Clasen, L. S., Lee, N. R., and Giedd, J. N.
- Published
- 2014
- Full Text
- View/download PDF
11. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (Nature Genetics, (2018), 50, 1, (26-41), 10.1038/s41588-017-0011-x)
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Turcot, V., Lu, Y., Highland, H. M., Schurmann, C., Justice, A. E., Fine, R. S., Bradfield, J. P., Esko, T., Giri, A., Graff, M., Guo, X., Hendricks, A. E., Karaderi, T., Lempradl, A., Locke, A. E., Mahajan, A., Marouli, E., Sivapalaratnam, S., Young, K. L., Alfred, T., Feitosa, M. F., Masca, N. G. D., Manning, A. K., Medina-Gomez, C., Mudgal, P., M. C. Y., Ng, Reiner, A. P., Vedantam, S., Willems, S. M., Winkler, T. W., Abecasis, G., Aben, K. K., Alam, D. S., Alharthi, S. E., Marchiori, Allison, Amouyel, P., Asselbergs, F. W., Auer, P. L., Balkau, B., Bang, L. E., Barroso, I., Bastarache, L., Benn, M., Bergmann, S., Bielak, L. F., Bluher, M., Boehnke, M., Boeing, H., Boerwinkle, E., Boger, C. A., Bork-Jensen, J., Bots, M. L., Bottinger, E. P., Bowden, D. W., Brandslund, I., Breen, G., Brilliant, M. H., Broer, L., Brumat, M., Burt, A. A., Butterworth, A. S., Campbell, P. T., Cappellani, S., Carey, D. J., Catamo, E., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Chowdhury, R., Christensen, C., Chu, A. Y., Cocca, M., Collins, F. S., Cook, J. P., Corley, J., Galbany, J. C., Cox, A. J., Crosslin, D. S., Cuellar-Partida, G., D'Eustacchio, A., Danesh, J., Davies, G., Bakker, P. I. W., Groot, M. C. H., Mutsert, R., Deary, I. J., Dedoussis, G., Demerath, E. W., Heijer, M., Hollander, A. I., Ruijter, H. M., Dennis, J. G., Denny, J. C., Di Angelantonio, E., Drenos, F., Du, M., Dube, M. -P., Dunning, A. M., Easton, D. F., Edwards, T. L., Ellinghaus, D., Ellinor, P. T., Elliott, P., Evangelou, E., Farmaki, A. -E., Farooqi, I. S., Faul, J. D., Fauser, S., Feng, S., Ferrannini, E., Ferrieres, J., Florez, J. C., Ford, I., Fornage, M., Franco, O. H., Franke, A., Franks, P. W., Friedrich, N., Frikke-Schmidt, R., Galesloot, T. E., Gan, W., Gandin, I., Gasparini, P., Gibson, J., Giedraitis, V., Gjesing, A. P., Gordon-Larsen, P., Gorski, M., Grabe, H. -J., Grant, S. F. A., Grarup, N., Griffiths, H. L., Grove, M. L., Gudnason, V., Gustafsson, S., Haessler, J., Hakonarson, H., Hammerschlag, A. R., Hansen, T., Harris, K. M., Harris, T. B., Hattersley, A. T., Have, C. T., Hayward, C., He, L., Heard-Costa, N. L., Heath, A. C., Heid, I. M., Helgeland, O., Hernesniemi, J., Hewitt, A. W., Holmen, O. L., Hovingh, G. K., Howson, J. M. M., Hu, Y., Huang, P. L., Huffman, J. E., Ikram, M. A., Ingelsson, E., Jackson, A. U., Jansson, J. -H., Jarvik, G. P., Jensen, G. B., Jia, Y., Johansson, S., Jorgensen, M. E., Jorgensen, T., Jukema, J. W., Kahali, B., Kahn, R. S., Kahonen, M., Kamstrup, P. R., Kanoni, S., Kaprio, J., Karaleftheri, M., Kardia, S. L. R., Karpe, F., Kathiresan, S., Kee, F., Kiemeney, L. A., Kim, E., Kitajima, H., Komulainen, P., Kooner, J. S., Kooperberg, C., Korhonen, T., Kovacs, P., Kuivaniemi, H., Kutalik, Z., Kuulasmaa, K., Kuusisto, J., Laakso, M., Lakka, T. A., Lamparter, D., Lange, E. M., Lange, L. A., Langenberg, C., Larson, E. B., Lee, N. R., Lehtimaki, T., Lewis, C. E., Li, H., Li, J., Li-Gao, R., Lin, H., Lin, K. -H., Lin, L. -A., Lin, X., Lind, L., Lindstrom, J., Linneberg, A., Liu, C. -T., Liu, D. J., Liu, Y., K. S., Lo, Lophatananon, A., Lotery, A. J., Loukola, A., Luan, J., Lubitz, S. A., Lyytikainen, L. -P., Mannisto, S., Marenne, G., Mazul, A. L., Mccarthy, M. I., McKean-Cowdin, R., Medland, S. E., Meidtner, K., Milani, L., Mistry, V., Mitchell, P., Mohlke, K. L., Moilanen, L., Moitry, M., Montgomery, G. W., Mook-Kanamori, D. O., Moore, C., Mori, T. A., Morris, A. D., Morris, A. P., Muller-Nurasyid, M., Munroe, P. B., Nalls, M. A., Narisu, N., Nelson, C. P., Neville, M., Nielsen, S. F., Nikus, K., Njolstad, P. R., Nordestgaard, B. G., Nyholt, D. R., O'Connel, J. R., O'Donoghue, M. L., Loohuis, L. M. O., Ophoff, R. A., Owen, K. R., Packard, C. J., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pasterkamp, G., Patel, A. P., Pattie, A., Pedersen, O., Peissig, P. L., Peloso, G. M., Pennell, C. E., Perola, M., Perry, J. A., Perry, J. R. B., Pers, T. H., Person, T. N., Peters, A., Petersen, E. R. B., Peyser, P. A., Pirie, A., Polasek, O., Polderman, T. J., Puolijoki, H., Raitakari, O. T., Rasheed, A., Rauramaa, R., Reilly, D. F., Renstrom, F., Rheinberger, M., Ridker, P. M., Rioux, J. D., Rivas, M. A., Roberts, D. J., Robertson, N. R., Robino, A., Rolandsson, O., Rudan, I., Ruth, K. S., Saleheen, D., Salomaa, V., Samani, N. J., Sapkota, Y., Sattar, N., Schoen, R. E., Schreiner, P. J., Schulze, M. B., Scott, R. A., Segura-Lepe, M. P., Shah, S. H., Sheu, W. H. -H., Sim, X., Slater, A. J., Small, K. S., Smith, A. V., Southam, L., Spector, T. D., Speliotes, E. K., Starr, J. M., Stefansson, K., Steinthorsdottir, V., Stirrups, K. E., Strauch, K., Stringham, H. M., Stumvoll, M., Sun, L., Surendran, P., Swift, A. J., Tada, H., Tansey, K. E., Tardif, J. -C., Taylor, K. D., Teumer, A., Thompson, D. J., Thorleifsson, G., Thorsteinsdottir, U., Thuesen, B. H., Tonjes, A., Tromp, G., Trompet, S., Tsafantakis, E., Tuomilehto, J., Tybjaerg-Hansen, A., Tyrer, J. P., Uher, R., Uitterlinden, A. G., Uusitupa, M., Laan, S. W., Duijn, C. M., Leeuwen, N., van Setten, J., Vanhala, M., Varbo, A., Varga, T. V., Varma, R., Edwards, D. R. V., Vermeulen, S. H., Veronesi, G., Vestergaard, H., Vitart, V., Vogt, T. F., Volker, U., Vuckovic, D., Wagenknecht, L. E., Walker, M., Wallentin, L., Wang, F., Wang, C. A., Wang, S., Wang, Y., Ware, E. B., Wareham, N. J., Warren, H. R., Waterworth, D. M., Wessel, J., White, H. D., Willer, C. J., Wilson, J. G., Witte, D. R., Wood, A. R., Wu, Y., Yaghootkar, H., Yao, J., Yao, P., Yerges-Armstrong, L. M., Young, R., Zeggini, E., Zhan, X., Zhang, W., Zhao, J. H., Zhao, W., Zhou, W., Zondervan, K. T., Rotter, J. I., Pospisilik, J. A., Rivadeneira, F., Borecki, I. B., Deloukas, P., Frayling, T. M., Lettre, G., North, K. E., Lindgren, C. M., Hirschhorn, J. N., Loos, R. J. F., Turcot, V., Lu, Y., Highland, H. M., Schurmann, C., Justice, A. E., Fine, R. S., Bradfield, J. P., Esko, T., Giri, A., Graff, M., Guo, X., Hendricks, A. E., Karaderi, T., Lempradl, A., Locke, A. E., Mahajan, A., Marouli, E., Sivapalaratnam, S., Young, K. L., Alfred, T., Feitosa, M. F., Masca, N. G. D., Manning, A. K., Medina-Gomez, C., Mudgal, P., Ng, M. C. Y., Reiner, A. P., Vedantam, S., Willems, S. M., Winkler, T. W., Abecasis, G., Aben, K. K., Alam, D. S., Alharthi, S. E., Marchiori, Allison, Amouyel, P., Asselbergs, F. W., Auer, P. L., Balkau, B., Bang, L. E., Barroso, I., Bastarache, L., Benn, M., Bergmann, S., Bielak, L. F., Bluher, M., Boehnke, M., Boeing, H., Boerwinkle, E., Boger, C. A., Bork-Jensen, J., Bots, M. L., Bottinger, E. P., Bowden, D. W., Brandslund, I., Breen, G., Brilliant, M. H., Broer, L., Brumat, M., Burt, A. A., Butterworth, A. S., Campbell, P. T., Cappellani, S., Carey, D. J., Catamo, E., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Chowdhury, R., Christensen, C., Chu, A. Y., Cocca, M., Collins, F. S., Cook, J. P., Corley, J., Galbany, J. C., Cox, A. J., Crosslin, D. S., Cuellar-Partida, G., D'Eustacchio, A., Danesh, J., Davies, G., Bakker, P. I. W., Groot, M. C. H., Mutsert, R., Deary, I. J., Dedoussis, G., Demerath, E. W., Heijer, M., Hollander, A. I., Ruijter, H. M., Dennis, J. G., Denny, J. C., Di Angelantonio, E., Drenos, F., Du, M., Dube, M. -P., Dunning, A. M., Easton, D. F., Edwards, T. L., Ellinghaus, D., Ellinor, P. T., Elliott, P., Evangelou, E., Farmaki, A. -E., Farooqi, I. S., Faul, J. D., Fauser, S., Feng, S., Ferrannini, E., Ferrieres, J., Florez, J. C., Ford, I., Fornage, M., Franco, O. H., Franke, A., Franks, P. W., Friedrich, N., Frikke-Schmidt, R., Galesloot, T. E., Gan, W., Gandin, I., Gasparini, P., Gibson, J., Giedraitis, V., Gjesing, A. P., Gordon-Larsen, P., Gorski, M., Grabe, H. -J., Grant, S. F. A., Grarup, N., Griffiths, H. L., Grove, M. L., Gudnason, V., Gustafsson, S., Haessler, J., Hakonarson, H., Hammerschlag, A. R., Hansen, T., Harris, K. M., Harris, T. B., Hattersley, A. T., Have, C. T., Hayward, C., He, L., Heard-Costa, N. L., Heath, A. C., Heid, I. M., Helgeland, O., Hernesniemi, J., Hewitt, A. W., Holmen, O. L., Hovingh, G. K., Howson, J. M. M., Hu, Y., Huang, P. L., Huffman, J. E., Ikram, M. A., Ingelsson, E., Jackson, A. U., Jansson, J. -H., Jarvik, G. P., Jensen, G. B., Jia, Y., Johansson, S., Jorgensen, M. E., Jorgensen, T., Jukema, J. W., Kahali, B., Kahn, R. S., Kahonen, M., Kamstrup, P. R., Kanoni, S., Kaprio, J., Karaleftheri, M., Kardia, S. L. R., Karpe, F., Kathiresan, S., Kee, F., Kiemeney, L. A., Kim, E., Kitajima, H., Komulainen, P., Kooner, J. S., Kooperberg, C., Korhonen, T., Kovacs, P., Kuivaniemi, H., Kutalik, Z., Kuulasmaa, K., Kuusisto, J., Laakso, M., Lakka, T. A., Lamparter, D., Lange, E. M., Lange, L. A., Langenberg, C., Larson, E. B., Lee, N. R., Lehtimaki, T., Lewis, C. E., Li, H., Li, J., Li-Gao, R., Lin, H., Lin, K. -H., Lin, L. -A., Lin, X., Lind, L., Lindstrom, J., Linneberg, A., Liu, C. -T., Liu, D. J., Liu, Y., Lo, K. S., Lophatananon, A., Lotery, A. J., Loukola, A., Luan, J., Lubitz, S. A., Lyytikainen, L. -P., Mannisto, S., Marenne, G., Mazul, A. L., Mccarthy, M. I., McKean-Cowdin, R., Medland, S. E., Meidtner, K., Milani, L., Mistry, V., Mitchell, P., Mohlke, K. L., Moilanen, L., Moitry, M., Montgomery, G. W., Mook-Kanamori, D. O., Moore, C., Mori, T. A., Morris, A. D., Morris, A. P., Muller-Nurasyid, M., Munroe, P. B., Nalls, M. A., Narisu, N., Nelson, C. P., Neville, M., Nielsen, S. F., Nikus, K., Njolstad, P. R., Nordestgaard, B. G., Nyholt, D. R., O'Connel, J. R., O'Donoghue, M. L., Loohuis, L. M. O., Ophoff, R. A., Owen, K. R., Packard, C. J., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pasterkamp, G., Patel, A. P., Pattie, A., Pedersen, O., Peissig, P. L., Peloso, G. M., Pennell, C. E., Perola, M., Perry, J. A., Perry, J. R. B., Pers, T. H., Person, T. N., Peters, A., Petersen, E. R. B., Peyser, P. A., Pirie, A., Polasek, O., Polderman, T. J., Puolijoki, H., Raitakari, O. T., Rasheed, A., Rauramaa, R., Reilly, D. F., Renstrom, F., Rheinberger, M., Ridker, P. M., Rioux, J. D., Rivas, M. A., Roberts, D. J., Robertson, N. R., Robino, A., Rolandsson, O., Rudan, I., Ruth, K. S., Saleheen, D., Salomaa, V., Samani, N. J., Sapkota, Y., Sattar, N., Schoen, R. E., Schreiner, P. J., Schulze, M. B., Scott, R. A., Segura-Lepe, M. P., Shah, S. H., Sheu, W. H. -H., Sim, X., Slater, A. J., Small, K. S., Smith, A. V., Southam, L., Spector, T. D., Speliotes, E. K., Starr, J. M., Stefansson, K., Steinthorsdottir, V., Stirrups, K. E., Strauch, K., Stringham, H. M., Stumvoll, M., Sun, L., Surendran, P., Swift, A. J., Tada, H., Tansey, K. E., Tardif, J. -C., Taylor, K. D., Teumer, A., Thompson, D. J., Thorleifsson, G., Thorsteinsdottir, U., Thuesen, B. H., Tonjes, A., Tromp, G., Trompet, S., Tsafantakis, E., Tuomilehto, J., Tybjaerg-Hansen, A., Tyrer, J. P., Uher, R., Uitterlinden, A. G., Uusitupa, M., Laan, S. W., Duijn, C. M., Leeuwen, N., van Setten, J., Vanhala, M., Varbo, A., Varga, T. V., Varma, R., Edwards, D. R. V., Vermeulen, S. H., Veronesi, G., Vestergaard, H., Vitart, V., Vogt, T. F., Volker, U., Vuckovic, D., Wagenknecht, L. E., Walker, M., Wallentin, L., Wang, F., Wang, C. A., Wang, S., Wang, Y., Ware, E. B., Wareham, N. J., Warren, H. R., Waterworth, D. M., Wessel, J., White, H. D., Willer, C. J., Wilson, J. G., Witte, D. R., Wood, A. R., Wu, Y., Yaghootkar, H., Yao, J., Yao, P., Yerges-Armstrong, L. M., Young, R., Zeggini, E., Zhan, X., Zhang, W., Zhao, J. H., Zhao, W., Zhou, W., Zondervan, K. T., Rotter, J. I., Pospisilik, J. A., Rivadeneira, F., Borecki, I. B., Deloukas, P., Frayling, T. M., Lettre, G., North, K. E., Lindgren, C. M., Hirschhorn, J. N., and Loos, R. J. F.
- Subjects
Publisher correction - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2019
12. Cloning and sequence analyses of a 2,3-dihydroxybiphenyl 1,2-dioxygenase gene (bphC) from Comamonas sp. SMN4 for phylogenetic and structural analysis
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Lee, N. R., Kwon, D. Y., and Min, K. H.
- Published
- 2003
- Full Text
- View/download PDF
13. Replication of LIN28B SNP association with age of menarche in young Filipino women
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Croteau-Chonka, D. C., Lange, L. A., Lee, N. R., Adair, L. S., and Mohlke, K. L.
- Published
- 2013
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- View/download PDF
14. Linear IgA bullous dermatosis following autologous PBSC transplantation in a patient with non-Hodgkin's lymphoma
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Yhim, H Y, Kwon, D H, Lee, N R, Song, E K, Yim, C Y, and Kwak, J Y
- Published
- 2011
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15. PROGNOSTIC FACTORS OF RENAL COLLECTING DUCT CARCINOMA BASED ON CLINICAL FEATURES AND EFFECTIVE CHEMOTHERAPY
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Kwon, K. A., Oh, S. Y., Kim, H. Y., Kim, T. M., Lim, H. Y., Lee, N.-R., Lee, H. J., Hong, S. H., and Rha, S. Y.
- Published
- 2012
16. § Social marketing as a strategy to increase immunization rates
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Opel, D J, Diekema, D S, Lee, N R, and Marcuse, E K
- Published
- 2009
17. Updated profiles of everyday executive function in youth with Down syndrome using the BRIEF‐2.
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Csumitta, K. D., Stephan, C. M., LaQuaglia, R. I., Miller, E., and Lee, N. R.
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EXECUTIVE function ,STATISTICS ,HUMAN research subjects ,DOWN syndrome ,AGE distribution ,HEALTH outcome assessment ,INFORMED consent (Medical law) ,SEX distribution ,QUESTIONNAIRES ,DESCRIPTIVE statistics ,DATA analysis ,ADOLESCENCE - Abstract
Background: Executive function difficulties in youth with Down syndrome (DS) are well recognised using informant‐report measures. However, the profile of relative challenges and strengths has not yet been evaluated using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF‐2), which includes a new internal factor structure. Method: Using the BRIEF‐2, profiles of everyday parent‐reported executive function (EF) were evaluated in youth with DS (n = 34) and compared with age‐based and sex‐based norms. EF profiles were also compared across raters (parent vs. teacher, n = 20) and relative to mental age‐matched typically developing controls (ns = 19 in each group). Results: Although within‐group differences were not revealed on indexes, significant differences were found among BRIEF‐2 scales. Across raters, teachers reported significantly more difficulties than parents. Compared with mental age‐matched typically developing controls, the DS group was rated more poorly on some but not all BRIEF‐2 scales. Conclusions: At the scale, but not the index level, the BRIEF‐2 identifies a variegated EF profile in children with DS. For several of the scales, significant differences were noted relative to both chronological age expectations (using norms) and mental‐age expectations (using a developmentally matched comparison group). At the scale level, the BRIEF‐2 continues to be a sensitive tool for identifying executive function difficulties as well as profiles of relative strengths and weaknesses in children with DS. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Interethnic analyses of blood pressure loci in populations of East Asian and European descent
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Takeuchi, F. (Fumihiko), Akiyama, M. (Masato), Matoba, N. (Nana), Katsuya, T. (Tomohiro), Nakatochi, M. (Masahiro), Tabara, Y. (Yasuharu), Narita, A. (Akira), Saw, W.-Y. (Woei-Yuh), Moon, S. (Sanghoon), Spracklen, C. N. (Cassandra N.), Chai, J.-F. (Jin-Fang), Kim, Y.-J. (Young-Jin), Zhang, L. (Liang), Wang, C. (Chaolong), Li, H. (Huaixing), Li, H. (Honglan), Wu, J.-Y. (Jer-Yuarn), Dorajoo, R. (Rajkumar), Nierenberg, J. L. (Jovia L.), Wang, Y. X. (Ya Xing), He, J. (Jing), Bennett, D. A. (Derrick A.), Takahashi, A. (Atsushi), Momozawa, Y. (Yukihide), Hirata, M. (Makoto), Matsuda, K. (Koichi), Rakugi, H. (Hiromi), Nakashima, E. (Eitaro), Isono, M. (Masato), Shirota, M. (Matsuyuki), Hozawa, A. (Atsushi), Ichihara, S. (Sahoko), Matsubara, T. (Tatsuaki), Yamamoto, K. (Ken), Kohara, K. (Katsuhiko), Igase, M. (Michiya), Han, S. (Sohee), Gordon-Larsen, P. (Penny), Huang, W. (Wei), Lee, N. R. (Nanette R.), Adair, L. S. (Linda S.), Hwang, M. Y. (Mi Yeong), Lee, J. (Juyoung), Chee, M. L. (Miao Li), Sabanayagam, C. (Charumathi), Zhao, W. (Wanting), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), Sun, L. (Liang), Huo, S. (Shaofeng), Edwards, T. L. (Todd L.), Long, J. (Jirong), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Friedlander, Y. (Yechiel), Kelly, T. N. (Tanika N.), Wei, W. B. (Wen Bin), Xu, L. (Liang), Cai, H. (Hui), Xiang, Y.-B. (Yong-Bing), Lin, K. (Kuang), Clarke, R. (Robert), Walters, R. G. (Robin G.), Millwood, I. Y. (Iona Y.), Li, L. (Liming), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), Elliott, P. (Paul), van der Harst, P. (Pim), T. I. (The International Genomics of Blood Pressure (iGEN-BP) Consortium), Chen, Z. (Zhengming), Sasaki, M. (Makoto), Shu, X.-O. (Xiao-Ou), Jonas, J. B. (Jost B.), He, J. (Jiang), Heng, C.-K. (Chew-Kiat), Chen, Y.-T. (Yuan-Tsong), Wong, T. Y. (Tien Yin), Sim, X. (Xueling), Mohlke, K. L. (Karen L.), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Miki, T. (Tetsuro), Nabika, T. (Toru), Yokota, M. (Mitsuhiro), Kamatani, Y. (Yoichiro), Kubo, M. (Michiaki), and Kato, N. (Norihiro)
- Abstract
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP. Acknowledgements Marie Loh71,72 (Institute of Health Sciences, University of Oulu, P.O.Box 5000FI-90014 Oulu, Finland and Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK), Niek Verweij73 (Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Weihua Zhang72,74 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK and Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK), Benjamin Lehne72 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK), Irene Mateo Leach73 (Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Alexander Drong75 (Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK), James Abbott76 (Bioinformatics Support Service, Imperial College London, South Kensington, London SW7 2AZ, UK), Sian-Tsung Tan74,77 (Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK and National Heart and Lung Institute, Imperial College London, London W12 0NN, UK), William R. Scott72,77 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK and Lung Institute, Imperial College London, London W12 0NN, UK), Gianluca Campanella72 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK), Marc Chadeau-Hyam72 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK), Uzma Afzal72,74 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK and Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK), Tõnu Esko78,79,80,81 (Estonian Genome Center, University of Tartu, Riia 23c, 51010 Tartu, Estonia and Division of Endocrinology, Children’s Hospital Boston, Longwood 300, Boston, MA 02115, USA and Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA and Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA), Sarah E. Harris82,83 (Medical Genetics Section, University of Edinburgh Molecular Medicine Centre and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK and Centre for Cognitive Aging and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK), Jaana Hartiala84,85 (Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA 90033, USA and Institute for Genetic Medicine, USC Keck School of Medicine, Los Angeles, CA 90033, USA), Marcus E. Kleber86 (Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany), Richa Saxena87 (Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA), Alexandre F.R. Stewart88,89 (University of Ottawa Heart Institute, Cardiovascular Research Methods Centre, Ontario K1Y 4W7, Canada and Ruddy Canadian Cardiovascular Genetics Centre, Ontario K1Y 4W7, Canada), Tarunveer S. Ahluwalia90 (Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark), Imke Aits91 (Institute of Epidemiology and Biobank Popgen, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany), Alexessander Da Silva Couto Alves92 (Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London SW7 2AZ, UK), Shikta Das92 (Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London SW7 2AZ, UK), Jemma C. Hopewell93 (Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK), Robert W. Koivula94 (Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, SE-205 02 Malmö, Sweden), Leo-Pekka Lyytikäinen95,96 (Department of Clinical Chemistry, Fimlab Laboratories, FI-33520 Tampere, Finland and Department of Clinical Chemistry, University of Tampere School of Medicine, FI-33014 Tampere, Finland), Iris Postmus97,98 (Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, Netherlands and Netherlands Consortium for Healthy Ageing, Leiden 2333 ZC, Netherlands), Olli T. Raitakari99,100 (Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, FI-20521 Turku, Finland and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FI-20520 Turku, Finland), Robert A. Scott101 (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK), Rossella Sorice102 (Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, 80131 Naples, Italy), Vinicius Tragante103 (Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands), Michela Traglia104,105 (Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy and Institute for Maternal and Child Health—IRCCS ‘‘Burlo Garofolo’’—Trieste, 34137 Trieste, Italy), Jon White106 (UCL Genetics Institute, Department of Genetics, Environment and Evolution, UCL, London WC1E 6BT, UK), Inês Barroso107,108,109 (Metabolic Disease Group, The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK and University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK), Andrew Bjonnes87 (Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA), Rory Collins103 (Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands), Gail Davies110 (Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK), Graciela Delgado86 (Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany), Pieter A. Doevendans103 (Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands), Lude Franke111 (Department of Genetics, University Medical Center, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Ron T. Gansevoort112 (Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Tanja B. Grammer86 (Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany), Niels Grarup86 (Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany), Jagvir Grewal72,74 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK and Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK), Anna-Liisa Hartikainen113,114 (Department of Obstetrics and Gynecology, University Hospital of Oulu, University of Oulu, Oulu FI-90014, Finland and Department of Clinical Sciences/Obsterics and Gynecology, University of Oulu, Oulu FI-90014, Finland), Stanley L. Hazen115,116 (Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH 44195, USA and Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA), Chris Hsu117 (Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA), Lise L.N. Husemoen118 (Research Centre for Prevention and Health, Glostrup University Hospital, 2600 Glostrup, Denmark), Johanne M. Justesen90 (Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark), Meena Kumari119 (Department of Epidemiology and Public Health, UCL, London WC1E 6BT, UK), Wolfgang Lieb91 (Institute of Epidemiology and Biobank Popgen, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany), David C.M. Liewald110 (Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK), Evelin Mihailov78 (Estonian Genome Center, University of Tartu, Riia 23c, 51010 Tartu, Estonia), Lili Milani78 (Estonian Genome Center, University of Tartu, Riia 23c, 51010 Tartu, Estonia), Rebecca Mills74 (Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK), Nina Mononen95,96 (Department of Clinical Chemistry, Fimlab Laboratories, FI-33520 Tampere, Finland and Department of Clinical Chemistry, University of Tampere School of Medicine, FI-33014 Tampere, Finland), Kjell Nikus120 (Heart Centre, Department of Cardiology, Tampere University Hospital, and University of Tampere School of Medicine, FI-33521 Tampere, Finland), Teresa Nutile102 (Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, 80131 Naples, Italy), Sarah Parish93 (Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK), Olov Rolandsson121 (Department of Public Health & Clinical Medicine, Section for Family Medicine, Umeå universitet, SE-901 85 Umeå, Sweden), Daniela Ruggiero102 (Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, 80131 Naples, Italy), Cinzia F. Sala104 (Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy), Harold Snieder122 (Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Thomas H.W. Spasø90 (Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark), Wilko Spiering123 (Department of Vascular Medicine, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands), John M. Starr83,124 (Centre for Cognitive Aging and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK and Alzheimer Scotland Dementia Research Centre, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK), David J. Stott125 (Academic Section of Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow G4 0SF, UK), Daniel O. Stram117 (Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA), Silke Szymczak126 (Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel 24105, Germany), W.H.Wilson Tang115,116 (Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH 44195, USA and Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA), Stella Trompet127 (Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, Netherlands), Väinö Turjanmaa128,129 (Department of Clinical Physiology, Tampere University Hospital, FI-33521 Tampere, Finland and Department of Clinical Physiology, University of Tampere School of Medicine, FI-33014 Tampere, Finland), Marja Vaarasmaki130 (Department of Obstetrics and Gynecology, Oulu University Hospital, PO Box 23FI-90029 Oulu, Finland), Wiek H. van Gilst73 (Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Dirk J. van Veldhuisen73 (Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Jorma S. Viikari131,132 (Department of Medicine, Turku University Hospital, FI-20521 Turku, Finland and Department of Medicine, University of Turku, FI-20014 Turku, Finland), Folkert W. Asselbergs103,133,134 (Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands and Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, 3511 GC Utrecht, Netherlands and Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London WC1E 6BT, UK), Marina Ciullo102 (Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, 80131 Naples, Italy), Andre Franke126 (Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel 24105, Germany), Paul W. Franks94,121,135 (Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, SE-205 02 Malmö, Sweden and Department of Public Health & Clinical Medicine, Section for Family Medicine, Umeå universitet, SE-901 85 Umeå, Sweden and Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA), Steve Franks136 (Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London W120HS, UK), Myron D. Gross137 (School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA), Torben Hansen90 (Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark), Marjo-Riitta Jarvelin72,92,138,139,140 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK and Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London SW7 2AZ, UK and Biocenter Oulu, University of Oulu, P.O. Box 5000 Aapistie 5A, FI-90014 Oulu, Finland and Unit of Primary Care, Oulu University Hospital, Kajaanintie 50 P.O.Box 20FI-90220 Oulu, Finland and Department of Children and Young People and Families, National Institute for Health and Welfare, Aapistie 1, Box 310, FI-90101 Oulu, Finland), Torben Jørgensen118 (Research Centre for Prevention and Health, Glostrup University Hospital, 2600 Glostrup, Denmark), Wouter J. Jukema127,133,141 (Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, Netherlands and Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, 3511 GC Utrecht, Netherlands and Interuniversity Cardiology Institute of the Netherlands, Utrecht 3511 EP, Netherlands), Mika Kähönen128,129 (Department of Clinical Physiology, Tampere University Hospital, FI-33521 Tampere, Finland and Department of Clinical Physiology, University of Tampere School of Medicine, FI-33014 Tampere, Finland), Mika Kivimaki119 (Department of Epidemiology and Public Health, UCL, London WC1E 6BT, UK), Terho Lehtimäki95,96 (Department of Clinical Chemistry, Fimlab Laboratories, FI-33520 Tampere, Finland and Department of Clinical Chemistry, University of Tampere School of Medicine, FI-33014 Tampere, Finland), Allan Linneberg118 (Research Centre for Prevention and Health, Glostrup University Hospital, 2600 Glostrup, Denmark), Oluf Pedersen90 (Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark), Nilesh J. Samani142,143 (Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK and National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK), Daniela Toniolo104,144 (Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy and Institute of Molecular GeneticsCNR, 27100 Pavia, Italy), Hooman Allayee84,85 (Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA 90033, USA and Institute for Genetic Medicine, USC Keck School of Medicine, Los Angeles, CA 90033, USA), Ian J. Deary83,110 (Centre for Cognitive Aging and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK and Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK), Winfried März86,145,146 (Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria and Synlab Academy, Synlab Services GmbH, Gottlieb-Daimler-Straße 25, 68165 Mannheim, Germany), Andres Metspalu78 (Estonian Genome Center, University of Tartu, Riia 23c, 51010 Tartu, Estonia), Cisca Wijmenga111 (Department of Genetics, University Medical Center, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Bruce H.W. Wolffenbuttel147 (Department of Endocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands), Paolo Vineis72 (Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK), Soterios A. KyrtopoulosNational Hellenic Research Foundation, Institute of Biological Research and Biotechnology, Athens 116 35, Greece), Jos C.S. Kleinjans149 (Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, 6229ER Maastricht, Netherlands), Mark I. McCarthy75,150 (Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK and Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK), James Scott77 (National Heart and Lung Institute, Imperial College London, London W12 0NN, UK)
- Published
- 2018
19. Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay
- Author
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Yoon, N. Y., primary, Wang, H. Y., additional, Jun, M., additional, Jung, M., additional, Kim, D. H., additional, Lee, N. R., additional, Hong, K.-W., additional, Seo, S. J., additional, Choi, E., additional, Lee, J., additional, Lee, H., additional, and Choi, E. H., additional
- Published
- 2018
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20. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- Author
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Justice, A. E. (Anne E.), Winkler, T. W. (Thomas W.), Feitosa, M. F. (Mary F.), Graff, M. (Misa), Fisher, V. A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J. S. (Julius S.), Ahluwalia, T. S. (Tarunveer S.), Chu, A. Y. (Audrey Y.), Heard-Costa, N. L. (Nancy L.), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J. D. (John D.), Kutalik, Z. (Zoltan), Xue, L. (Luting), Mahajan, A. (Anubha), Renstrom, F. (Frida), Wu, J. (Joseph), Qi, Q. (Qibin), Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L. F. (Lawrence F.), Bonnefond, A. (Amelie), Bragg, J. (Jennifer), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M. N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J. E. (Jennifer E.), Jackson, A. U. (Anne U.), Justesen, J. M. (Johanne Marie), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M. E. (Marcus E.), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R. P. (Rita P. S.), Mueller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A. V. (Albert Vernon), Smith, J. A. (Jennifer A.), Stancakova, A. (Alena), Strawbridge, R. J. (Rona J.), Stringham, H. M. (Heather M.), Sung, Y. J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), van der Laan, S. W. (Sander W.), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vedantam, S. L. (Sailaja L.), Verweij, N. (Niek), Vink, J. M. (Jacqueline M.), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zimmermann, M. E. (Martina E.), Zubair, N. (Niha), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S. J. (Stephan J. L.), Bartz, T. M. (Traci M.), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bottinger, E. (Erwin), Braga, D. (Daniele), Buckley, B. M. (Brendan M.), Buyske, S. (Steve), Campbell, H. (Harry), Chambers, J. C. (John C.), Collins, F. S. (Francis S.), Curran, J. E. (Joanne E.), de Borst, G. J. (Gert J.), de Craen, A. J. (Anton J. M.), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Delgado, G. E. (Graciela E.), den Ruijter, H. M. (Hester M.), Eiriksdottir, G. (Gudny), Eriksson, A. L. (Anna L.), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Goran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T. B. (Tamara B.), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. D. (Nicholas D.), Heath, A. C. (Andrew C.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Hollensted, M. (Mette), Holmen, O. L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Järvelin, M.-R. (Marjo-Riitta), Jhun, M. A. (Min A.), Jorgensen, M. E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Kramer, B. K. (Bernhard K.), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Leander, K. (Karin), Lee, N. R. (Nanette R.), Lind, L. (Lars), Lindgren, C. M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stephane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P. A. (Pamela A. F.), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N. G. (Nicholas G.), McKenzie, C. A. (Colin A.), McKnight, B. (Barbara), Mellstrom, D. (Dan), Menni, C. (Cristina), Montgomery, G. W. (Grant W.), Musk, A. W. (A. W. (Bill)), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P. A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D. J. (David J.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Rice, T. (Treva), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Bien, S. A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R. A. (Robert A.), Sennblad, B. (Bengt), Siemelink, M. A. (Marten A.), Silbernagel, G. (Gunther), Slagboom, P. E. (P. Eline), Snieder, H. (Harold), Staessen, J. A. (Jan A.), Stott, D. J. (David J.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Taylor, K. D. (Kent D.), Tayo, B. O. (Bamidele O.), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Volzke, H. (Henry), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Waldenberger, M. (Melanie), Westendorp, R. G. (R. G. J.), Wild, S. (Sarah), Willemsen, G. (Gonneke), Wolffenbuttel, B. H. (Bruce H. R.), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zhao, W. (Wei), Zillikens, M. C. (M. Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Boger, C. A. (Carsten A.), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Bruinenberg, M. (Marcel), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Chines, P. S. (Peter S.), Cooper, R. S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), de Faire, U. (Ulf), Ferrucci, L. (Luigi), Franks, P. W. (Paul W.), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.-J. (Hans-Jorgen), Gudnason, V. (Vilmundur), Haiman, C. A. (Christopher A.), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A. D. (Andrew D.), Jukema, W. (Wouter), Kardia, S. L. (Sharon L. R.), Kivimäki, M. (Mika), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), Marz, W. (Winfried), McCarthy, M. I. (Mark I.), Metspalu, A. (Andres), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Palmer, L. J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B. H. (Blair H.), Sorensen, T. I. (Thorkild I. A.), Strauch, K. (Konstantin), Tiemeier, H. (Henning), Tremoli, E. (Elena), Van der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wilson, J. F. (James F.), Tyrrell, J. (Jessica), Frayling, T. M. (Timothy M.), Barroso, I. (Ines), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C. S. (Caroline S.), Hirschhorn, J. N. (Joel N.), Hunter, D. J. (David J.), Spector, T. D. (Tim D.), Strachan, D. P. (David P.), van Duijn, C. M. (Cornelia M.), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Marchini, J. (Jonathan), Loos, R. J. (Ruth J. F.), Kilpeläinen, T. O. (Tuomas O.), Liu, C.-T. (Ching-Ti), Borecki, I. B. (Ingrid B.), North, K. E. (Kari E.), Cupples, L. A. (L. Adrienne), Justice, A. E. (Anne E.), Winkler, T. W. (Thomas W.), Feitosa, M. F. (Mary F.), Graff, M. (Misa), Fisher, V. A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J. S. (Julius S.), Ahluwalia, T. S. (Tarunveer S.), Chu, A. Y. (Audrey Y.), Heard-Costa, N. L. (Nancy L.), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J. D. (John D.), Kutalik, Z. (Zoltan), Xue, L. (Luting), Mahajan, A. (Anubha), Renstrom, F. (Frida), Wu, J. (Joseph), Qi, Q. (Qibin), Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L. F. (Lawrence F.), Bonnefond, A. (Amelie), Bragg, J. (Jennifer), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M. N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J. E. (Jennifer E.), Jackson, A. U. (Anne U.), Justesen, J. M. (Johanne Marie), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M. E. (Marcus E.), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R. P. (Rita P. S.), Mueller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A. V. (Albert Vernon), Smith, J. A. (Jennifer A.), Stancakova, A. (Alena), Strawbridge, R. J. (Rona J.), Stringham, H. M. (Heather M.), Sung, Y. J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), van der Laan, S. W. (Sander W.), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vedantam, S. L. (Sailaja L.), Verweij, N. (Niek), Vink, J. M. (Jacqueline M.), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zimmermann, M. E. (Martina E.), Zubair, N. (Niha), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S. J. (Stephan J. L.), Bartz, T. M. (Traci M.), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bottinger, E. (Erwin), Braga, D. (Daniele), Buckley, B. M. (Brendan M.), Buyske, S. (Steve), Campbell, H. (Harry), Chambers, J. C. (John C.), Collins, F. S. (Francis S.), Curran, J. E. (Joanne E.), de Borst, G. J. (Gert J.), de Craen, A. J. (Anton J. M.), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Delgado, G. E. (Graciela E.), den Ruijter, H. M. (Hester M.), Eiriksdottir, G. (Gudny), Eriksson, A. L. (Anna L.), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Goran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T. B. (Tamara B.), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. D. (Nicholas D.), Heath, A. C. (Andrew C.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Hollensted, M. (Mette), Holmen, O. L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Järvelin, M.-R. (Marjo-Riitta), Jhun, M. A. (Min A.), Jorgensen, M. E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Kramer, B. K. (Bernhard K.), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Leander, K. (Karin), Lee, N. R. (Nanette R.), Lind, L. (Lars), Lindgren, C. M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stephane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P. A. (Pamela A. F.), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N. G. (Nicholas G.), McKenzie, C. A. (Colin A.), McKnight, B. (Barbara), Mellstrom, D. (Dan), Menni, C. (Cristina), Montgomery, G. W. (Grant W.), Musk, A. W. (A. W. (Bill)), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P. A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D. J. (David J.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Rice, T. (Treva), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Bien, S. A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R. A. (Robert A.), Sennblad, B. (Bengt), Siemelink, M. A. (Marten A.), Silbernagel, G. (Gunther), Slagboom, P. E. (P. Eline), Snieder, H. (Harold), Staessen, J. A. (Jan A.), Stott, D. J. (David J.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Taylor, K. D. (Kent D.), Tayo, B. O. (Bamidele O.), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Volzke, H. (Henry), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Waldenberger, M. (Melanie), Westendorp, R. G. (R. G. J.), Wild, S. (Sarah), Willemsen, G. (Gonneke), Wolffenbuttel, B. H. (Bruce H. R.), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zhao, W. (Wei), Zillikens, M. C. (M. Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Boger, C. A. (Carsten A.), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Bruinenberg, M. (Marcel), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Chines, P. S. (Peter S.), Cooper, R. S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), de Faire, U. (Ulf), Ferrucci, L. (Luigi), Franks, P. W. (Paul W.), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.-J. (Hans-Jorgen), Gudnason, V. (Vilmundur), Haiman, C. A. (Christopher A.), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A. D. (Andrew D.), Jukema, W. (Wouter), Kardia, S. L. (Sharon L. R.), Kivimäki, M. (Mika), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), Marz, W. (Winfried), McCarthy, M. I. (Mark I.), Metspalu, A. (Andres), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Palmer, L. J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B. H. (Blair H.), Sorensen, T. I. (Thorkild I. A.), Strauch, K. (Konstantin), Tiemeier, H. (Henning), Tremoli, E. (Elena), Van der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wilson, J. F. (James F.), Tyrrell, J. (Jessica), Frayling, T. M. (Timothy M.), Barroso, I. (Ines), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C. S. (Caroline S.), Hirschhorn, J. N. (Joel N.), Hunter, D. J. (David J.), Spector, T. D. (Tim D.), Strachan, D. P. (David P.), van Duijn, C. M. (Cornelia M.), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Marchini, J. (Jonathan), Loos, R. J. (Ruth J. F.), Kilpeläinen, T. O. (Tuomas O.), Liu, C.-T. (Ching-Ti), Borecki, I. B. (Ingrid B.), North, K. E. (Kari E.), and Cupples, L. A. (L. Adrienne)
- Abstract
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
- Published
- 2017
21. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
- Author
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Ehret, G. B. (Georg B.), Ferreira, T. (Teresa), Chasman, D. I. (Daniel I.), Jackson, A. U. (Anne U.), Schmidt, E. M. (Ellen M.), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'an), Donnelly, L. A. (Louise A.), Kanoni, S. (Stavroula), Petersen, A. -. (Ann -Kristin), Pihurl, V. (Vasyl), Strawbridge, R. J. (Rona J.), Shungin, D. (Dmitry), Hughes, M. F. (Maria F.), Meirelles, O. (Osorio), Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M. E. (Marcus E.), Guo, X. (Xiuqing), Lyytikainen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Nidas), Nolte, I. M. (Ilja M.), Magnusson, P. K. (Patrik K.), Salfati, E. L. (Elias L.), Rallidis, L. S. (Loukianos S.), Theusch, E. (Elizabeth), Smith, A. J. (Andrew J. P.), Folkersen, L. (Lasse), Witkowska, K. (Kate), Pers, T. H. (Tune H.), Joehanes, R. (Roby), Kim, S. K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R. (Rick), Johnson, A. D. (Andrew D.), Warren, H. (Helen), Kim, Y. J. (Young Jin), Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. O. (Bamidele O.), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L. S. (Linda S.), Amin, N. (Najaf), Arkingl, D. E. (Dan E.), Axelsson, T. (Tomas), Baldassarre, D. (Damian), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M. R. (Michael R.), Barroso, I. (Ines), Bevan, S. (Stephen), Bis, J. C. (Joshua C.), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Boomsma, D. I. (Dorret I.), Bornstein, S. R. (Stefan R.), Brown, M. J. (Morris J.), Burnier, M. (Michel), Cabrera, C. P. (Claudia P.), Chambers, J. C. (John C.), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P. S. (Peter S.), Chung, R.-H. (Ren-Hua), Collins, F. S. (Francis S.), Connell, J. M. (John M.), Doring, A. (Angela), Dallongeville, J. (Jean), Danesh, J. (John), de Faire, U. (Ulf), Delgado, G. (Graciela), Dominiczak, A. F. (Anna F.), Doney, A. S. (Alex S. F.), Drenos, F. (Fotios), Edkins, S. (Sarah), Eicher, J. D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tonu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fai, T. (Tove), Farra, M. (Martin), Felixl, J. F. (Janine F.), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschinil, N. (Nora), Franco, O. H. (Oscar H.), Franco-Cereceda, A. (Anders), Fraser, R. M. (Ross M.), Ganesh, S. K. (Santhi K.), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goe, A. (Anuj), Goodall, A. H. (Alison H.), Goodarzi, M. (Mark), Gorski, M. (Mathias), Grassler, J. (Jurgen), Groves, C. J. (Christopher J.), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Goran), Hartikainen, A.-L. (Anna-Liisa), Hassinen, M. (Maija), Havulinna, A. S. (Aki S.), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.-H. (Karl-Heinz), Hicks, A. A. (Andrew A.), Hingorani, A. D. (Aroon D.), Hirschhorn, J. N. (Joel N.), Hofmanl, A. (Albert), Holmen, J. (Jostein), Holmen, O. L. (Oddgeir Lingaas), Hottenga, J.-J. (Jouke-Jan), Howard, P. (Phil), Hsiung, C. A. (Chao A.), Hunt, S. C. (Steven C.), Ikram, M. A. (M. Arfan), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R. A. (Richard A.), Kahonen, M. (Mika), Kang, H. M. (Hyun Min), Kathiresan, S. (Sekar), Keating, B. J. (Brendan J.), Khaw, K.-T. (Kay-Tee), Kim, Y. K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J. S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R. M. (Ronald M.), Kuh, D. (Diana), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Lee, N. R. (Nanette R.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindstrom, J. (Jaana), Lobbens, S. (Stephane), Mannisto, S. (Satu), Muller, G. (Gabriele), Muller-Nurasyid, M. (Martina), Mach, F. (Francois), Markus, H. S. (Hugh S.), Marouli, E. (Eirini), McCarthy, M. I. (Mark I.), McKenzie, C. A. (Colin A.), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M. E. (May E.), Morris, A. D. (Andrew D.), Morrison, A. C. (Alanna C.), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C. J. (Christopher J.), O'Reilly, P. F. (Paul F.), Ong, K. K. (Ken K.), Paccaud, F. (Fred), Palmer, C. D. (Cameron D.), Parsa, A. (Afshin), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W.), Perola, M. (Markus), Peters, A. (Annette), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Psaty, B. M. (Bruce M.), Quertermous, T. (Thomas), Rao, D. C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N. W. (N. William), Renstrom, F. (Frida), Rettig, R. (Rainer), Rice, K. M. (Kenneth M.), Roberts, R. (Robert), Rose, L. M. (Lynda M.), Rossouw, J. (Jacques), Samani, N. J. (Nilesh J.), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W. H. (Wayne H-H), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smit, J. H. (Johannes H.), Smith, A. V. (Albert V.), Sosa, M. X. (Maria X.), Spector, T. D. (Tim D.), Stancakova, A. (Alena), Stanton, A. V. (Alice V.), Stirrups, K. E. (Kathleen E.), Stringham, H. M. (Heather M.), Sundstrom, J. (Johan), Swift, A. J. (Amy J.), Syvanen, A.-C. (Ann-Christine), Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K. V. (Kirill V.), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M. D. (Martin D.), Tremoli, E. (Elena), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), van Duijn, C. M. (Cornelia M.), van Iperen, E. P. (Erik P. A.), Vasan, R. S. (Ramachandran S.), Verwoert, G. C. (Germaine C.), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B. F. (Benjamin F.), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L. V. (Louise V.), Wareham, N. J. (Nicholas J.), Watldns, H. (Hugh), Weder, A. B. (Alan B.), Westra, H. J. (Harm Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J. F. (James F.), Wong, T. Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jie), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R. S. (Richard S.), Mohlke, K. L. (Karen L.), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, H. J. (Hinco J.), Willer, C. J. (Cristen J.), Franke, L. (Lude), Hovingh, G. K. (G. Kees), Taylor, K. D. (Kent D.), Dedoussis, G. (George), Sever, P. (Peter), Wong, A. (Andrew), Lind, L. (Lars), Assimes, T. L. (Themistocles L.), Njolstad, I. (Inger), Schwarz, P. E. (Peter E. H.), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. J. (Mark J.), Melander, E. (E.), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimaki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), Marz, W. (Winfried), Kumar, M. (Meena), Salomaa, V. (Veikko), Chen, Y. I. (Yii-Der I.), Rotter, J. I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. G. (Edward G.), Kuulasmaa, K. (Kari), Franks, P. W. (Paul W.), Hamsten, A. (Anders), Wichmann, H.-E. (H-Erich), Palmer, C. N. (Colin N. A.), Stefansson, K. (Kari), Ridker, P. M. (Paul M.), Loos, R. J. (Ruth J. F.), Chalcravarti, A. (Aravinda), Deloukas, P. (Panos), Morris, A. P. (Andrew P.), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), Ehret, G. B. (Georg B.), Ferreira, T. (Teresa), Chasman, D. I. (Daniel I.), Jackson, A. U. (Anne U.), Schmidt, E. M. (Ellen M.), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'an), Donnelly, L. A. (Louise A.), Kanoni, S. (Stavroula), Petersen, A. -. (Ann -Kristin), Pihurl, V. (Vasyl), Strawbridge, R. J. (Rona J.), Shungin, D. (Dmitry), Hughes, M. F. (Maria F.), Meirelles, O. (Osorio), Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M. E. (Marcus E.), Guo, X. (Xiuqing), Lyytikainen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Nidas), Nolte, I. M. (Ilja M.), Magnusson, P. K. (Patrik K.), Salfati, E. L. (Elias L.), Rallidis, L. S. (Loukianos S.), Theusch, E. (Elizabeth), Smith, A. J. (Andrew J. P.), Folkersen, L. (Lasse), Witkowska, K. (Kate), Pers, T. H. (Tune H.), Joehanes, R. (Roby), Kim, S. K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R. (Rick), Johnson, A. D. (Andrew D.), Warren, H. (Helen), Kim, Y. J. (Young Jin), Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. O. (Bamidele O.), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L. S. (Linda S.), Amin, N. (Najaf), Arkingl, D. E. (Dan E.), Axelsson, T. (Tomas), Baldassarre, D. (Damian), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M. R. (Michael R.), Barroso, I. (Ines), Bevan, S. (Stephen), Bis, J. C. (Joshua C.), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Boomsma, D. I. (Dorret I.), Bornstein, S. R. (Stefan R.), Brown, M. J. (Morris J.), Burnier, M. (Michel), Cabrera, C. P. (Claudia P.), Chambers, J. C. (John C.), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P. S. (Peter S.), Chung, R.-H. (Ren-Hua), Collins, F. S. (Francis S.), Connell, J. M. (John M.), Doring, A. (Angela), Dallongeville, J. (Jean), Danesh, J. (John), de Faire, U. (Ulf), Delgado, G. (Graciela), Dominiczak, A. F. (Anna F.), Doney, A. S. (Alex S. F.), Drenos, F. (Fotios), Edkins, S. (Sarah), Eicher, J. D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tonu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fai, T. (Tove), Farra, M. (Martin), Felixl, J. F. (Janine F.), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschinil, N. (Nora), Franco, O. H. (Oscar H.), Franco-Cereceda, A. (Anders), Fraser, R. M. (Ross M.), Ganesh, S. K. (Santhi K.), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goe, A. (Anuj), Goodall, A. H. (Alison H.), Goodarzi, M. (Mark), Gorski, M. (Mathias), Grassler, J. (Jurgen), Groves, C. J. (Christopher J.), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Goran), Hartikainen, A.-L. (Anna-Liisa), Hassinen, M. (Maija), Havulinna, A. S. (Aki S.), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.-H. (Karl-Heinz), Hicks, A. A. (Andrew A.), Hingorani, A. D. (Aroon D.), Hirschhorn, J. N. (Joel N.), Hofmanl, A. (Albert), Holmen, J. (Jostein), Holmen, O. L. (Oddgeir Lingaas), Hottenga, J.-J. (Jouke-Jan), Howard, P. (Phil), Hsiung, C. A. (Chao A.), Hunt, S. C. (Steven C.), Ikram, M. A. (M. Arfan), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R. A. (Richard A.), Kahonen, M. (Mika), Kang, H. M. (Hyun Min), Kathiresan, S. (Sekar), Keating, B. J. (Brendan J.), Khaw, K.-T. (Kay-Tee), Kim, Y. K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J. S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R. M. (Ronald M.), Kuh, D. (Diana), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Lee, N. R. (Nanette R.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindstrom, J. (Jaana), Lobbens, S. (Stephane), Mannisto, S. (Satu), Muller, G. (Gabriele), Muller-Nurasyid, M. (Martina), Mach, F. (Francois), Markus, H. S. (Hugh S.), Marouli, E. (Eirini), McCarthy, M. I. (Mark I.), McKenzie, C. A. (Colin A.), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M. E. (May E.), Morris, A. D. (Andrew D.), Morrison, A. C. (Alanna C.), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C. J. (Christopher J.), O'Reilly, P. F. (Paul F.), Ong, K. K. (Ken K.), Paccaud, F. (Fred), Palmer, C. D. (Cameron D.), Parsa, A. (Afshin), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W.), Perola, M. (Markus), Peters, A. (Annette), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Psaty, B. M. (Bruce M.), Quertermous, T. (Thomas), Rao, D. C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N. W. (N. William), Renstrom, F. (Frida), Rettig, R. (Rainer), Rice, K. M. (Kenneth M.), Roberts, R. (Robert), Rose, L. M. (Lynda M.), Rossouw, J. (Jacques), Samani, N. J. (Nilesh J.), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W. H. (Wayne H-H), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smit, J. H. (Johannes H.), Smith, A. V. (Albert V.), Sosa, M. X. (Maria X.), Spector, T. D. (Tim D.), Stancakova, A. (Alena), Stanton, A. V. (Alice V.), Stirrups, K. E. (Kathleen E.), Stringham, H. M. (Heather M.), Sundstrom, J. (Johan), Swift, A. J. (Amy J.), Syvanen, A.-C. (Ann-Christine), Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K. V. (Kirill V.), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M. D. (Martin D.), Tremoli, E. (Elena), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), van Duijn, C. M. (Cornelia M.), van Iperen, E. P. (Erik P. A.), Vasan, R. S. (Ramachandran S.), Verwoert, G. C. (Germaine C.), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B. F. (Benjamin F.), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L. V. (Louise V.), Wareham, N. J. (Nicholas J.), Watldns, H. (Hugh), Weder, A. B. (Alan B.), Westra, H. J. (Harm Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J. F. (James F.), Wong, T. Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jie), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R. S. (Richard S.), Mohlke, K. L. (Karen L.), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, H. J. (Hinco J.), Willer, C. J. (Cristen J.), Franke, L. (Lude), Hovingh, G. K. (G. Kees), Taylor, K. D. (Kent D.), Dedoussis, G. (George), Sever, P. (Peter), Wong, A. (Andrew), Lind, L. (Lars), Assimes, T. L. (Themistocles L.), Njolstad, I. (Inger), Schwarz, P. E. (Peter E. H.), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. J. (Mark J.), Melander, E. (E.), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimaki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), Marz, W. (Winfried), Kumar, M. (Meena), Salomaa, V. (Veikko), Chen, Y. I. (Yii-Der I.), Rotter, J. I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. G. (Edward G.), Kuulasmaa, K. (Kari), Franks, P. W. (Paul W.), Hamsten, A. (Anders), Wichmann, H.-E. (H-Erich), Palmer, C. N. (Colin N. A.), Stefansson, K. (Kari), Ridker, P. M. (Paul M.), Loos, R. J. (Ruth J. F.), Chalcravarti, A. (Aravinda), Deloukas, P. (Panos), Morris, A. P. (Andrew P.), Newton-Cheh, C. (Christopher), and Munroe, P. B. (Patricia B.)
- Abstract
To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure–associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure–related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
- Published
- 2016
22. Genetic studies of body mass index yield new insights for obesity biology
- Author
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E., Kahali B., Berndt S. I., Justice A. E., Pers T. H., Day F. R., Powell C., Vedantam S., Buchkovich M. L., Yang J., Croteau-Chonka D. C., Esko T., Fall T., Ferreira T., Gustafsson S., Kutalik Z., Luan J., Magi R., Randall J. C., Winkler T. W., Wood A. R., Workalemahu T., Faul J. D., Smith J. A., Zhao J. H., Zhao W., Chen J., Fehrmann R., Hedman A. K., Karjalainen J., Schmidt E. M., Absher D., Amin N., Anderson D., Beekman M., Bolton J. L., Bragg-Gresham J. L., Buyske S., Demirkan A., Deng G., Ehret G. B., Feenstra B., Feitosa M. F., Fischer K., Goel A., Gong J., Jackson A. U., Kanoni S., Kleber M. E., Kristiansson K., Lim U., Lotay V., Mangino M., Leach I. M., Medina-Gomez C., Medland S. E., Nalls M. A., Palmer C. D., Pasko D., Pechlivanis S., Peters M. J., Prokopenko I., Shungin D., Stancakova A., Strawbridge R. J., Sung Y. J., Tanaka T., Teumer A., Trompet S., van der Laan S. W., van Setten J., Van Vliet-Ostaptchouk J. V., Wang Z., Yengo L., Zhang W., Isaacs A., Albrecht E., Arnlov J., Arscott G. M., Attwood A. P., Bandinelli S., Barrett A., Bas I. N., Bellis C., Bennett A. J., Berne C., Blagieva R., Bluher M., Bohringer S., Bonnycastle L. L., Bottcher Y., Boyd H. A., Bruinenberg M., Caspersen I. H., Chen Y. I., Clarke R., Daw E. W., de Craen A. J. M., Delgado G., Dimitriou M., Doney A. S. F., Eklund N., Estrada K., Eury E., Folkersen L., Fraser R. M., Garcia M. E., Geller F., Giedraitis V., Gigante B., Go A. S., Golay A., Goodall A. H., Gordon S. D., Gorski M., Grabe H. J., Grallert H., Grammer T. B., Grassler J., Gronberg H., Groves C. J., Gusto G., Haessler J., Hall P., Haller T., Hallmans G., Hartman C. A., Hassinen M., Hayward C., Heard-Costa N. L., Helmer Q., Hengstenberg C., Holmen O., Hottenga J. J., James A. L., Jeff J. M., Johansson A., Jolley J., Juliusdottir T., Kinnunen L., Koenig W., Koskenvuo M., Kratzer W., Laitinen J., Lamina C., Leander K., Lee N. R., Lichtner P., Lind L., Lindstrom J., Lo K. S., Lobbens S., Lorbeer R., Lu Y., Mach F., Magnusson P. K. E., Mahajan A., McArdle W. L., McLachlan S., Menni C., Merger S., Mihailov E., Milani L., Moayyeri A., Monda K. L., Morken M. A., Mulas A., Muller G., Muller-Nurasyid M., Musk A. W., Nagaraja R., Nothen M. M., Nolte I. M., Pilz S., Rayner N. W., Renstrom F., Rettig R., Ried J. S., Ripke S., Robertson N. R., Rose L. M., Sanna S., Scharnagl H., Scholtens S., Schumacher F. R., Scott W. R., Seufferlein T., Shi J., Smith A. V., Smolonska J., Stanton A. V., Steinthorsdottir V., Stirrups K., Stringham H. M., Sundstrom J., Swertz M. A., Swift A. J., Syvanen A. C., Tan S. T., Tayo B. O., Thorand B., Thorleifsson G., Tyrer J. P., Uh H. W., Vandenput L., Verhulst F. C., Vermeulen S. H., Verweij N., Vonk J. M., Waite L. L., Warren H. R., Waterworth D., Weedon M. N., Wilkens L. R., Willenborg C., Wilsgaard T., Wojczynski M. K., Wong A., Wright A. F., Zhang Q., Brennan E. P., Choi M., Dastani Z., Drong A. W., Eriksson P., Franco-Cereceda A., Gadin J. R., Gharavi A. G., Goddard M. E., Handsaker R. E., Huang J., Karpe F., Kathiresan S., Keildson S., Kiryluk K., Kubo M., Lee J. Y., Liang L., Lifton R. P., Ma B., McCarroll S. A., McKnight A. J., Min J. L., Moffatt M. F., Montgomery G. W., Murabito J. M., Nicholson G., Nyholt D. R., Okada Y., Perry J. R. B., Dorajoo R., Reinmaa E., Salem R. M., Sandholm N., Scott R. A., Stolk L., Takahashi A., Van't Hooft F. M., Vinkhuyzen A. A. E., Westra H. J., Zheng W., Zondervan K. T., Heath A. C., Arveiler D., Bakker S. J. L., Beilby J., Bergman R. N., Blangero J., Bovet P., Campbell H., Caulfield M. J., Cesana G., Chakravarti A., Chasman D. I., Chines P. S., Collins F. S., Crawford D. C., Cupples L. A., Cusi D., Danesh J., de Faire U., Den Ruijter H. M., Dominiczak A. F., Erbel R., Erdmann J., Eriksson J. G., Farrall M., Felix S. B., Ferrannini E., Ferrieres J., Ford I., Forouhi N. G., Forrester T., Franco O. H., Gansevoort R. T., Gejman P. V., Gieger C., Gottesman O., Gudnason V., Gyllensten U., Hall A. S., Harris T. B., Hattersley A. T., Hicks A. A., Hindorff L. A., Hingorani A. D., Hofman A., Homuth G., Hovingh G. K., Humphries S. E., Hunt S. C., Hypponen E., Illig T., Jacobs K. B., Jarvelin M. R., Jockel K. H., Johansen B., Jousilahti P., Jukema J. W., Jula A. M., Kaprio J., Kastelein J. J. P., Keinanen-Kiukaanniemi S. M., Kiemeney L. A., Knekt P., Kooner J. S., Kooperberg C., Kovacs P., Kraja A. T., Kumari M., Kuusisto J., Lakka T. A., Langenberg C., Marchand L. L., Lehtimaki T., Lyssenko V., Mannisto S., Marette A., Matise T. C., McKenzie C. A., McKnight B., Moll F. L., Morris A. D., Morris A. P., Murray J. C., Nelis M., Ohlsson C., Oldehinkel A. J., Ong K. K., Madden P. A. F., Pasterkamp G., Peden J. F., Peters A., Postma D. S., Pramstaller P. P., Price J. F., Qi L., Raitakari O. T., Rankinen T., Rao D. C., Rice T. K., Ridker P. M., Rioux J. D., Ritchie M. D., Rudan I., Salomaa V., Samani N. J., Saramies J., Sarzynski M. A., Schunkert H., Schwarz P. E. H., Sever P., Shuldiner A. R., Sinisalo J., Stolk R. P., Strauch K., Tonjes A., Tregouet D. A., Tremblay A., Tremoli E., Virtamo J., Vohl M. C., Volker U., Waeber G., Willemsen G., Witteman J. C., Zillikens M. C., Adair L. S., Amouyel P., Asselbergs F. W., Assimes T. L., Bochud M., Boehm B. O., Boerwinkle E., Bornstein S. R., Bottinger E. P., Bouchard C., Cauchi S., Chambers J. C., Chanock S. J., Cooper R. S., de Bakker P. I. W., Dedoussis G., Ferrucci L., Franks P. W., Froguel P., Groop L. C., Haiman C. A., Hamsten A., Hui J., Hunter D. J., Hveem K., Kaplan R. C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N. G., Marz W., Melbye M., Metspalu A., Moebus S., Munroe P. B., Njolstad I., Oostra B. A., Palmer C. N. A., Pedersen N. L., Perola M., Perusse L., Peters U., Power C., Quertermous T., Rauramaa R., Rivadeneira F., Saaristo T. E., Saleheen D., Sattar N., Schadt E. E., Schlessinger D., Slagboom P. E., Snieder H., Spector T. D., Thorsteinsdottir U., Stumvoll M., Tuomilehto J., Uitterlinden A. G., Uusitupa M., van der Harst P., Walker M., Wallaschofski H., Wareham N. J., Watkins H., Weir D. R., Wichmann H. E., Wilson J. F., Zanen P., Borecki I. B., Deloukas P., Fox C. S., Heid I. M., O'connell J. R., Strachan D. P., Stefansson K., van Duijn C. M., Abecasis G. R., Franke L., Frayling T. M., McCarthy M. I., Visscher P. M., Scherag A., Willer C. J., Boehnke M., Mohlke K. L., Lindgren C. M., Beckmann J. S., Barroso I., North K. E., Ingelsson E., Hirschhorn J. N., Loos R. J. F., Speliotes E. K., Thompson J. R., Goldstein B. A., Konig I. R., Cazier J. B., Grundberg E., Havulinna A. S., Ho W. K., Hopewell J. C., Eriksson N., Lundmark P., Lyytikainen L. P., Rafelt S., Tikkanen E., Van Zuydam N., Voight B. F., Ziegler A., Altshuler D., Balmforth A. J., Braund P. S., Burgdorf C., Claudi-Boehm S., Cox D., Do R., Doney A. S., El Mokhtari N., Fontanillas P., Hager J., Han B. G., Hunt S. E., Kang H. M., Kessler T., Knowles J. W., Kolovou G., Langford C., Lokki M. L., Lundmark A., Meisinger C., Melander O., Maouche S., Nikus K., Rasheed A., Rosinger S., Rubin D., Rumpf M. P., Schafer A., Sivananthan M., Song C., Stewart A. F., Thorgeirsson G., van der Schoot C. E., Wagner P. J., Wells G. A., Wild P. S., Tsun-Po Y., Basart H. V., Brambilla P., Cambien F., Cupples A. L., Dehghan A., Diemert P., Epstein S. E., Evans A., Ferrario M., Gauguier D., Hazen S. L., Holm H., Iribarren C., Jang Y., Kahonen M., Kee F., Kim H. S., Klopp N., Kuulasmaa K., Laaksonen R., Ouwehand W. H., Parish S., Park J. E., Rader D. J., Shah S. H., Stark K., Wallentin L., Zimmermann M. E., Nieminen M. S., Sandhu M. S., Pastinen T., Zalloua P. A., Siegbahn A., Schreiber S., Ripatti S., Blankenberg S. S., O'donnell C. J., Reilly M., Collins R., Roberts R., Pattaro C., Kottgen A., Garnaas M., Boger C. A., Fuchsberger C., Olden M., Chen M. H., Tin A., Taliun D., Li M., Gao X., Yang Q., Hundertmark C., Foster M. C., O'seaghdha C. M., Glazer N. L., Liu C. T., Struchalin M., Li G., Johnson A. D., Gierman H. J., Hwang S. J., Atkinson E. J., Lohman K. K., Cornelis M. C., Chouraki V., Holliday E. G., Sorice R., Deshmukh H., Ulivi S., Chu A. Y., Murgia F., Imboden M., Kollerits B., Pistis G., Launer L. J., Aspelund T., Eiriksdottir G., Mitchell B. D., Schmidt H., Cavalieri M., Rao M., Hu F. B., de Andrade M., Turner S. T., Ding J., Andrews J. S., Freedman B. I., Doring A., Kolcic I., Zemunik T., Boban M., Minelli C., Wheeler H. E., Igl W., Zaboli G., Wild S. H., Ellinghaus D., Nothlings U., Jacobs G., Biffar R., Endlich K., Ernst F., Kroemer H. K., Nauck M., Stracke S., Volzke H., Aulchenko Y., Polasek O., Hastie N. D., Vitart V., Helmer C., Wang J. J., Ruggiero D., Bergmann S., Viikari J., Nikopensius T., Province M. A., Ketkar S., Colhoun H. M., Doney A., Robino A., Giulianini F., Kramer B. K., Portas L., Buckley B. M., Adam M., Thun G. A., Paulweber B., Haun M., Sala C., Metzger M., Mitchell P., Ciullo M., Kim S. K., Vollenweider P., Palmer C., Gasparini P., Pirastu M., Probst-Hensch N. M., Kronenberg F., Toniolo D., Coresh J., Schmidt R., Siscovick D. S., Kardia S. L., Curhan G., Franke A., Parsa A., Goessling W., Kao W. H., de Boer I. H., Peralta C. A., Akylbekova E., Kramer H., Arking D. E., Franceschini N., Egan J., Hernandez D. G., Townsend R. R., Lumley T., Psaty B. M., Kestenbaum B., Haritunians T., Mooser V., Florez J. C., Meigs J. B., Lu X., Leak T. S., Aasarod K., Skorpen F., Baumert J., Devuyst O., Mychaleckyj J. C., Kedenko L., Coassin S., Hallan S., Navis G., Shlipak M. G., Bull S. B., Paterson A. D., Rotter J. I., Dreisbach A. W., Anderson C. A., Guo Q., Henders A., Lambert A., Lee S. H., Kraft P., Kennedy S. H., Macgregor S., Missmer S. A., Painter J. N., Roseman F., Treloar S. A., Wallace L., Forsblom C., Isakova T., McKay G. J., Williams W. W., Sadlier D. M., Makinen V. P., Swan E. J., Boright A. P., Ahlqvist E., Keller B. J., Huang H., Ahola A., Fagerholm E., Gordin D., Harjutsalo V., He B., Heikkila O., Hietala K., Kyto J., Lahermo P., Lehto M., Osterholm A. M., Parkkonen M., Pitkaniemi J., Rosengard-Barlund M., Saraheimo M., Sarti C., Soderlund J., Soro-Paavonen A., Syreeni A., Thorn L. M., Tikkanen H., Tolonen N., Tryggvason K., Waden J., Gill G. V., Prior S., Guiducci C., Mirel D. B., Taylor A., Hosseini M., Parving H. H., Rossing P., Tarnow L., Ladenvall C., Alhenc-Gelas F., Lefebvre P., Rigalleau V., Roussel R., Maestroni A., Maestroni S., Falhammar H., Gu T., Mollsten A., Cimponeriu D., Mihai I., Mota M., Mota E., Serafinceanu C., Stavarachi M., Hanson R. L., Nelson R. G., Kretzler M., Panduru N. M., Gu H. F., Brismar K., Zerbini G., Hadjadj S., Marre M., Lajer M., Waggott D., Savage D. A., Bain S. C., Martin F., Godson C., Groop P. H., Maxwell A. P., Sengupta S., Peloso G. M., Ganna A., Mora S., Chang H. Y., Den Hertog H. M., Donnelly L. A., Freitag D. F., Gurdasani D., Heikkila K., Johnson T., Kaakinen M., Kettunen J., Li X., Montasser M. E., Petersen A. K., Saxena R., Service S. K., Sidore C., Surakka I., Teslovich T. M., Van den Herik E. G., Volcik K. A., Wu Y., Asiki G., Been L. F., Burnett M. S., Elliott P., Eyjolfsson G. I., Goodarzi M. O., Gravito M. L., Hartikainen A. L., Hung Y. J., Jones M. R., Kaleebu P., Khaw K. T., Kim E., Komulainen P., Lin S. Y., Narisu N., Nieminen T. V., Nsubuga R. N., Olafsson I., Palotie A., Papamarkou T., Pomilla C., Pouta A., Ruokonen A., Seeley J., Silander K., Tiret L., van Pelt L., Wainwright N., Wijmenga C., Young E. H., Bennett F., Boomsma D. I., Burnier M., Chen Y. D., Feranil A. B., Freimer N. B., Hsiung C. A., Kesaniemi A., Koudstaal P. J., Krauss R. M., Kyvik K. O., Meneton P., Moilanen L., Sanghera D. K., Sheu W. H., Whitfield J. B., Wolffenbuttel B. H., Ordovas J. M., Rich S. S., Johnson A., Johnson L., Larson M., Levy D., Newton-Cheh C., O'reilly P., Palmas W., Rice K., Smith A., Snider H., Tobin M., Verwoert G., Rice K. M., Verwoert G. C., Pihur V., Heath S., Sober S., Arora P., Zhang F., Lucas G., Milaneschi Y., Parker A. N., Fava C., Fox E. R., Go M. J., Sjogren M., Vinay D., Alexander M., Tabara Y., Shaw-Hawkins S., Whincup P. H., Shi G., Seielstad M., Sim X., Nguyen K. D., Matullo G., Gaunt T. R., Onland-Moret N. C., Cooper M. N., Platou C. G., Org E., Hardy R., Dahgam S., Palmen J., Kuznetsova T., Uiterwaal C. S., Adeyemo A., Ludwig B., Tomaszewski M., Tzoulaki I., Palmer N. D., Chang Y. P., Steinle N. I., Grobbee D. E., Morrison A. C., Najjar S., Hadley D., Brown M. J., Connell J. M., Day I. N., Lawlor D. A., Lawrence R. W., Ongen H., Li Y., Young J. H., Bis J. C., Bolton J. A., Chaturvedi N., Islam M., Jafar T. H., Kulkarni S. R., Howard P., Guarrera S., Ricceri F., Emilsson V., Plump A., Weder A. B., Sun Y. V., Scott L. J., Peltonen L., Vartiainen E., Brand S. M., Staessen J. A., Wang T. J., Burton P. R., Artigas M. S., Dong Y., Wang X., Zhu H., Rudock M. E., Heckbert S. R., Smith N. L., Wiggins K. L., Doumatey A., Shriner D., Veldre G., Viigimaa M., Kinra S., Prabhakaran D., Tripathy V., Langefeld C. D., Rosengren A., Thelle D. S., Corsi A. M., Singleton A., Hilton G., Salako T., Iwai N., Kita Y., Ogihara T., Ohkubo T., Okamura T., Ueshima H., Umemura S., Eyheramendy S., Meitinger T., Cho Y. S., Kim H. L., Scott J., Sehmi J. S., Hedblad B., Nilsson P., Smith G. D., Raffel L. J., Yao J., Schwartz S. M., Ikram M., W L., Mosley T. H., Seshadri S., Shrine N. R., Wain L. V., Zitting P., Cooper J. A., van Gilst W. H., Janipalli C. S., Mani K., Yajnik C. S., Mattace-Raso F. U., Lakatta E. G., Orru M., Scuteri A., Ala-Korpela M., Kangas A. J., Soininen P., Tukiainen T., Wurtz P., Ong R. T., Dorr M., Galan P., Hercberg S., Lathrop M., Zelenika D., Zhai G., Meschia J. F., Sharma P., Terzic J., Kumar M., Denniff M., Zukowska-Szczechowska E., Wagenknecht L. E., Fowkes F., Charchar F. J., Guo X., Rotimi C., Bots M. L., Brand E., Talmud P. J., Nyberg F., Laan M., Palmer L. J., van der Schouw Y. T., Casas J. P., Vineis P., Ganesh S. K., Wong T. Y., Tai E. S., Morris R. W., Marmot M. G., Miki T., Chandak G. R., Zhu X., Elosua R., Soranzo N., Sijbrands E. J., Uda M., Vasan R. S., Alizadeh B. Z., de Boer R. A., Boezen H. M., Hillege H. L., van der Klauw M. M., Ormel J., Rosmalen J. G., Slaets J. P., Lagou V., Welch R. P., Wheeler E., Rehnberg E., Rasmussen-Torvik L. J., Lecoeur C., Johnson P. C., Sennblad B., Salo P., Timpson N. J., Evans D. M., St Pourcain B., Bielak L. F., Horikoshi M., Navarro P., Raychaudhuri S., Chen H., Rybin D., Willems S. M., Song K., An P., Marullo L., Jansen H., Pankow J. S., Edkins S., Varga T. V., Oksa H., Antonella M., Kong A., Herder C., Antti J., Small K., Miljkovic I., Atalay M., Kiess W., Smit J. H., Campbell S., Fowkes G. R., Rathmann W., Maerz W., Watanabe R. M., de Geus E. J., Penninx B. W., Toenjes A., Peyser P. A., Korner A., Dupuis J., Cucca F., Balkau B., Bouatia-Naji N., Purcell S., Musunuru K., Ardissino D., Mannucci P. M., Anand S., Engert J. C., Morgan T., Spertus J. A., Stoll M., Girelli D., McKeown P. P., Patterson C. C., Merlini P. A., Berzuini C., Bernardinelli L., Peyvandi F., Tubaro M., Celli P., Fetiveau R., Marziliano N., Casari G., Galli M., Ribichini F., Rossi M., Bernardi F., Zonzin P., Piazza A., Yee J., Friedlander Y., Marrugat J., Subirana I., Sala J., Ramos R., Williams G., Nathan D. M., Macrae C. A., Berglund G., Asselta R., Duga S., Spreafico M., Daly M. J., Nemesh J., Korn J. M., Surti A., Gianniny L., Parkin M., Burtt N., Gabriel S. B., Wright B. J., Ball S. G., Schunkert I., Linsel-Nitschke P., Lieb W., Fischer M., Grosshennig A., Preuss M., Scholz M., Chen Z., Wilensky R., Matthai W., Qasim A., Hakonarson H. H., Devaney J., Pichard A. D., Kent K. M., Satler L., Lindsay J. M., Waksman R., Knouff C. W., Scheffold T., Berger K., Huge A., Martinelli N., Olivieri O., Corrocher R., Xie C., Ahmadi K. R., Ainali C., Bataille V., Bell J. T., Buil A., Dermitzakis E. T., Dimas A. S., Durbin R., Glass D., Hassanali N., Ingle C., Knowles D., Krestyaninova M., Lowe C. E., Meduri E., Di Meglio P., Montgomery S. B., Nestle F. O., Nica A. C., Nisbet J., O'rahilly S., Parts L., Potter S., Sekowska M., Shin S. Y., Surdulescu G., Travers M. E., Tsaprouni L., Tsoka S., Wilk A., Yang T. P., Higashio J., Williams R., Nato A., Ambite J. L., Deelman E., Manolio T., Heiss G., Taylor K., Avery C., Graff M., Lin D., Quibrera M., Cochran B., Kao L., Umans J., Cole S., Maccluer J., Person S., Gross M., Fornage M., Durda P., Jenny N., Patsy B., Arnold A., Buzkova P., Haines J., Murdock D., Glenn K., Brown-Gentry K., Thornton-Wells T., Dumitrescu L., Bush W. S., Mitchell S. L., Goodloe R., Wilson S., Boston J., Malinowski J., Restrepo N., Oetjens M., Fowke J., Spencer K., Pendergrass S., Le Marchand L., Park L., Tiirikainen M., Kolonel L., Cheng I., Wang H., Shohet R., Stram D., Henderson B., Monroe K., Anderson G., Carlson C., Prentice R., Lacroix A., Wu C., Carty C., Rosse S., Young A., Kocarnik J., Lin Y., Jackson R., Duggan D., Kuller L., He C., Sulem P., Barbalic M., Broer L., Byrne E. M., Gudbjartsson D. F., McArdle P. F., Porcu E., van Wingerden S. W., Zhuang W. V., Lauc L. B., Broekmans F. J., Burri A., Chen C., Corre T., Coviello A. D., D'adamo P., Davies G., Deary I. J., Ebrahim S., Fauser B. C., Ferreli L., Folsom A. R., Hankinson S. E., Hass M., Janssens A. C., Karasik D., Keyzer J., Kiel D. P., Lahti J., Lai S., Laisk T., Laven J. S., Liu J., Lopez L. M., Louwers Y. V., Marongiu M., Klaric I. M., Masciullo C., Melzer D., Newman A. B., Pare G., Peeters P. H., Pop V. J., Raikkonen K., Salumets A., Stacey S. N., Starr J. M., Stathopoulou M. G., Styrkarsdottir U., Tenesa A., Tryggvadottir L., Tsui K., van Dam R. M., van Gils C. H., van Nierop P., Vink J. M., Voorhuis M., Widen E., Wijnands-Van Gent C. J., Yerges-Armstrong L. M., Zgaga L., Zygmunt M., Buring J. E., Crisponi L., Demerath E. W., Streeten E. A., Murray A., Visser J. A., Lunetta K. L., Elks C. E., Cousminer D. L., Koller D. L., Lin P., Smith E. N., Warrington N. M., Alavere H., Berenson G. S., Blackburn H., Busonero F., Chen W., Couper D., Easton D. F., Eriksson J., Foroud T., Kilpelainen T. O., Li S., Murray S. S., Ness A. R., Northstone K., Peacock M., Pennell C. E., Pharoah P., Rafnar T., Rice J. P., Ring S. M., Schork N. J., Segre A. V., Sovio U., Srinivasan S. R., Tammesoo M. L., van Meurs J. B., Young L., Bierut L. J., and Econs M. J.
- Abstract
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
- Published
- 2015
23. Genome-Wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci
- Author
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Zhang, S., Chen, P., Gao, Y.-T., Wang, Y., Teo, Y. Y., Tai, E. S., Kim, Y. J., Kita, Y., Wu, Y., Tabara, Y., Yang, C.-F., Takeuchi, F., Gu, D., Lee, N. R., Zhang, Y., Go, M. J., Katsuya, T., Peng, H., Shu, X.-O., Chang, L.-C., Kelly, T. N., Nakashima, E., Li, C., Li, H., Adair, L. S., Zhao, Q., Chen, C.-H., Ohkubo, T., Nabika, T., Kim, N. H., Lu, L., and Edwards, T. L.
- Abstract
We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26,600 East Asian participants (stage-1) followed by replication study of up to 28,783 participants (stage-2). For novel loci, statistical significance was determined by a P
- Published
- 2013
- Full Text
- View/download PDF
24. Replication of LIN28B SNP association with age of menarche in young Filipino women: LIN28Bassociation with age of menarche
- Author
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Lee, N. R., Croteau-Chonka, D. C., Mohlke, K. L., Lange, L. A., and Adair, L. S.
- Abstract
Age of menarche, or the timing of first menses in girls, is a physiological trait that shows substantial genetic heritability. Earlier age of menarche is associated with increased childhood adiposity and with adult risk of obesity and cardiovascular disease. In 827 young Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS), we observed nominal association with age of menarche (β = −0.118 years, 95% confidence interval = (−0.216, −0.020), P = 0.019) for the single nucleotide polymorphism (SNP) rs7759938 from the menarche locus LIN28B with an effect direction consistent with the previous report. We also tested whether childhood adiposity, as measured by body mass index (BMI) at age 8, mediated the relationship between rs7759938 and age of menarche. We observed suggestive evidence that the effect of the SNP on age of menarche was independent of childhood adiposity. These data confirm the strongest gene reported in Europeans (LIN28B) as a contributor to age of menarche in an Asian population.
- Published
- 2013
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- View/download PDF
25. Appropriate non-carbapenems are not inferior to carbapenems as initial empirical therapy for bacteremia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a propensity score weighted multicenter cohort study.
- Author
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Ko, J.-H., Lee, N. R., Joo, E.-J., Moon, S.-y., Choi, J.-K., Park, D. A., and Peck, K. R.
- Subjects
- *
ENTEROBACTERIACEAE diseases , *ANTIBIOTIC synthesis , *CARBAPENEMS , *SCANNING electron microscopy , *ELECTRONIC health records , *DIAGNOSIS , *THERAPEUTICS - Abstract
The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B. [ABSTRACT FROM AUTHOR]
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- 2018
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26. Mapping the Stability of Human Brain Asymmetry across Five Sex-Chromosome Aneuploidies
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Lin, A., primary, Clasen, L., additional, Lee, N. R., additional, Wallace, G. L., additional, Lalonde, F., additional, Blumenthal, J., additional, Giedd, J. N., additional, and Raznahan, A., additional
- Published
- 2015
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27. Replication ofLIN28BSNP association with age of menarche in young Filipino women
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Croteau-Chonka, D. C., primary, Lange, L. A., additional, Lee, N. R., additional, Adair, L. S., additional, and Mohlke, K. L., additional
- Published
- 2013
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- View/download PDF
28. Control of Gal-Induced Antibody and NK Cell Activation Is Important for the Long-Term Survival of Porcine Pancreatic Islets in Non-Human Primates
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Kim, J.-S., primary, Lee, N.-R., additional, Nam, H.-Y., additional, Lim, H.-J., additional, Kim, Y.-H., additional, Shin, J.-S., additional, Lee, J.-I., additional, Kang, H.-J., additional, Jung, K.-C., additional, Park, S.-H., additional, Kim, S.-J., additional, and Park, C.-G., additional
- Published
- 2012
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29. Clinical Features in Renal Cell Cancer Patients in TKI ERA: An Analysis of Web-Based Registry Data, Korea Cancer Study Group, GU & GY Committee, KCSG GU10-12
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Kim, H.Y., primary, Lee, H.J., additional, Kim, H.S., additional, Kwon, K.A., additional, Lee, N.-R., additional, Sun, J.-M., additional, Park, K.H., additional, Koh, S.J., additional, Hong, S.H., additional, Bae, W.K., additional, Lee, S.-H., additional, Lee, J.-L., additional, Lim, H.Y., additional, and Rha, S.Y., additional
- Published
- 2012
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30. Distinct Cortical Correlates of Autistic versus Antisocial Traits in a Longitudinal Sample of Typically Developing Youth
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Wallace, G. L., primary, Shaw, P., additional, Lee, N. R., additional, Clasen, L. S., additional, Raznahan, A., additional, Lenroot, R. K., additional, Martin, A., additional, and Giedd, J. N., additional
- Published
- 2012
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31. Linear IgA bullous dermatosis following autologous PBSC transplantation in a patient with non-Hodgkin's lymphoma
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Yhim, H Y, primary, Kwon, D H, additional, Lee, N R, additional, Song, E K, additional, Yim, C Y, additional, and Kwak, J Y, additional
- Published
- 2010
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32. TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1
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Lee, C S, primary, Yi, J-S, additional, Jung, S-Y, additional, Kim, B-W, additional, Lee, N-R, additional, Choo, H-J, additional, Jang, S-Y, additional, Han, J, additional, Chi, S-G, additional, Park, M, additional, Lee, J-H, additional, and Ko, Y-G, additional
- Published
- 2010
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33. School-age outcomes of newborns treated for persistent pulmonary hypertension
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Rosenberg, A A, primary, Lee, N R, additional, Vaver, K N, additional, Werner, D, additional, Fashaw, L, additional, Hale, K, additional, and Waas, N, additional
- Published
- 2009
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34. A case-control study of brain structure and behavioral characteristics in 47, XXX syndrome.
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Lenroot, R. K., Blumenthal, J. D., Wallace, G. L., Clasen, L. S., Lee, N. R., and Giedd, J. N.
- Subjects
TRIPLE X syndrome ,X chromosome ,CHROMOSOME abnormalities ,NEUROANATOMY ,MAGNETIC resonance imaging of the brain ,CASE-control method - Abstract
Trisomy X, the presence of an extra X chromosome in females (47, XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age- and sex-matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention-deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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35. Investigation of microchannel wettability on the formation of droplets and efficient mixing in microfluidic devices
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Choi, C. -H, Naveen Prasad, Lee, N. -R, and Lee, C. -S
36. Kinetics-based inference of environment-dependent microbial interactions and their dynamic variation.
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Song H-S, Lee N-R, Kessell AK, McCullough HC, Park S-Y, Zhou K, and Lee D-Y
- Subjects
- Kinetics, Models, Biological, Environment, Microbial Interactions physiology, Escherichia coli metabolism
- Abstract
Microbial communities in nature are dynamically evolving as member species change their interactions subject to environmental variations. Accounting for such context-dependent dynamic variations in interspecies interactions is critical for predictive ecological modeling. In the absence of generalizable theoretical foundations, we lack a fundamental understanding of how microbial interactions are driven by environmental factors, significantly limiting our capability to predict and engineer community dynamics and function. To address this issue, we propose a novel theoretical framework that allows us to represent interspecies interactions as an explicit function of environmental variables (such as substrate concentrations) by combining growth kinetics and a generalized Lotka-Volterra model. A synergistic integration of these two complementary models leads to the prediction of alterations in interspecies interactions as the outcome of dynamic balances between positive and negative influences of microbial species in mixed relationships. The effectiveness of our method was experimentally demonstrated using a synthetic consortium of two Escherichia coli mutants that are metabolically dependent (due to an inability to synthesize essential amino acids) but competitively grow on a shared substrate. The analysis of the E. coli binary consortium using our model not only showed how interactions between the two amino acid auxotrophic mutants are controlled by the dynamic shifts in limiting substrates but also enabled quantifying previously uncharacterizable complex aspects of microbial interactions, such as asymmetry in interactions. Our approach can be extended to other ecological systems to model their environment-dependent interspecies interactions from growth kinetics.IMPORTANCEModeling environment-controlled interspecies interactions through separate identification of positive and negative influences of microbes in mixed relationships is a new capability that can significantly improve our ability to understand, predict, and engineer the complex dynamics of microbial communities. Moreover, the prediction of microbial interactions as a function of environmental variables can serve as valuable benchmark data to validate modeling and network inference tools in microbial ecology, the development of which has often been impeded due to the lack of ground truth information on interactions. While demonstrated against microbial data, the theory developed in this work is readily applicable to general community ecology to predict interactions among macroorganisms, such as plants and animals, as well as microorganisms., Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
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37. Applying core principles to the design and evaluation of the 'Take Charge. Take the Test' campaign: what worked and lessons learned.
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Fraze JL, Uhrig JD, Davis KC, Taylor MK, Lee NR, Spoeth S, Robinson A, Smith K, Johnston J, and McElroy L
- Subjects
- Female, Focus Groups, Humans, Interviews as Topic, Male, Mass Media, Social Marketing, Black or African American, HIV Seropositivity diagnosis, Mass Screening statistics & numerical data, Program Development, Program Evaluation
- Abstract
Objectives: To describe the application of seven core principles to the design and evaluation of a human immunodeficiency virus (HIV) testing social marketing campaign as a case study example., Study Design: The Centers for Disease Control and Prevention (CDC) used a structured social marketing approach, informed by the Ecological Model, the Theory of Planned Behaviour and the Health Belief Model, to develop and evaluate a two-city campaign with print, radio and outdoor advertising; HIV telephone hotlines; an HIV website; community partnerships; and events to promote information seeking and HIV testing., Methods: The CDC applied seven core principles to design and evaluate the campaign, including formative research, the use of behavioural theories, audience segmentation, message design and pretesting, channel selection, process evaluation and outcome evaluation., Results: Over 200 partners in both cities contributed significantly to campaign efforts. Key informant interviews indicated that, due to increased coordination, city infrastructures for HIV testing improved. More than 9600 individuals attended campaign events in both cities, with 1492 rapid HIV tests administered and 14 newly-identified HIV individuals. Overall, event attendees responded positively to campaign materials and events, and free HIV testing opportunities. The campaign significantly increased information-seeking behaviours in the form of hotline calls and web searches. Audience reaction and receptivity to the final campaign materials was very high. Exposure to campaign messages was associated with increases in key knowledge items, intentions to get tested, and peer-to-peer communication., Conclusions: The seven core principles, including formative research, behavioural theories and extensive partnerships, acted synergistically to help a campaign reach its target audience with compelling, relevant messages and motivate them to seek information and get an HIV test. Rapid testing removes many barriers by providing a testing process that can be accessed and acted upon quickly in response to media exposure. Findings suggest that modifying the campaign in future implementations to encourage the target audience to attend and participate in rapid testing events, while expanding the number and reach of such events, may have considerable potential to measurably increase testing behaviours.
- Published
- 2009
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38. Effects of substrates on biofilm formation observed by atomic force microscopy.
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Oh YJ, Lee NR, Jo W, Jung WK, and Lim JS
- Subjects
- Extracellular Matrix chemistry, Extracellular Matrix metabolism, Inorganic Chemicals, Microscopy, Atomic Force, Organic Chemicals, Pseudomonas aeruginosa growth & development, Pseudomonas aeruginosa ultrastructure, Bacterial Adhesion, Biofilms drug effects, Biofilms growth & development, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa physiology
- Abstract
Formation of biofilm is known to be strongly dependent on substrates including topography, materials, and chemical treatment. In this study, a variety of substrates are tested for understanding biofilm formation. Sheets of aluminum, steel, rubber, and polypropylene have been used to examine their effects on formation of Pseudomonas aeruginosa biofilm. In particular, the morphological variation, transition, and adhesiveness of biofilm were investigated through local measurement by atomic force microscopy (AFM). Mechanism of removing biofilm from adhering to substrate is also analyzed, thus the understanding of the mechanism can be potentially useful to prevent the biofilm formation. The results reveal that formation of biofilm can remain on rough surface regardless of substrates in hot water, which may easily induce extra-polymeric substances detachment from bacterial surface. By probing using AFM, local force-distance characterization of extra-cellular materials extracted from the bacteria can exhibit the progress of the biofilm formation and functional complexities.
- Published
- 2009
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39. Molecular cloning of the nahG gene encoding salicylate hydroxylase from Pseudomonas fluorescens.
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Chung YS, Lee NR, Cheon CL, Song ES, Lee MS, Kim Y, and Min KH
- Subjects
- Base Sequence, Cloning, Molecular, Conserved Sequence, Molecular Sequence Data, Restriction Mapping, Sequence Homology, Amino Acid, Mixed Function Oxygenases genetics, Pseudomonas fluorescens genetics
- Abstract
A gene encoding the salicylate hydroxylase was cloned from the genomic DNA of Pseudomonas fluorescens SME11. The DNA fragment containing the nahG gene for the salicylate hydroxylase was mapped with restriction endonucleases and sequenced. The DNA fragment contained an ORF of 1,305 bp encoding a polypeptide of 434 amino acid residues. The nucleotide and amino acid sequences of the salicylate hydroxylase revealed several conserved regions with those of the enzyme encoded in P. putida PpG7: The homology of the nucleotide sequence is 83% and that of amino acid sequence is 72%. We found large conserved regions of the amino acid sequence at FAD and NADH binding regions. The FAD binding site is located at the amino terminal region and a lysine residue functions as a NADH-binding site.
- Published
- 2001
40. Helicobacter pylori in dental plaque and saliva.
- Author
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Kim N, Lim SH, Lee KH, You JY, Kim JM, Lee NR, Jung HC, Song IS, and Kim CY
- Subjects
- Gastric Mucosa microbiology, Humans, Polymerase Chain Reaction, Sensitivity and Specificity, Dental Plaque microbiology, Helicobacter pylori isolation & purification, Saliva microbiology
- Abstract
Background: About half of the world population is infected with H. pylori, but the transmission and the source of this infection are still unclear. Recently, dental plaque (DP) and saliva have been implicated as possible sources of H. pylori infection. This study was done to investigate the detection rates of H. pylori in the DP and saliva by use of PCR depending on H. pylori infection state of gastric mucosa., Methods: In 46 subjects, gastric H. pylori colonization was evaluated with CLO test, microscopy of Gram stained mucosal smear, culture and histology after modified Giemsa staining in the antrum and body, respectively. A patient was regarded as H. pylori positive if one or more of the four aforementioned test methods demonstrated H. pylori colonization of the gastric mucosa. For detection of H. pylori in the DP and saliva, PCR assay was done with ET4-U and ET4-L primers. To estimate the sensitivity and specificity of this PCR, H. pylori positivity was evaluated in the antrum and body, separately., Results: The sensitivity of mucosal PCR was 50.0% (27/54) and the specificity 86.8% (33/38). When a subject was regarded as H. pyloi positive, if either antrum or body mucosal H. pylori was is positive, the positive rate of mucosal PCR was 62.1% (18 subjects) in the 29 H. pylori-positive and 17.6% (3 subjects) in the 17 H. pylori-negative subjects. DP PCR was positive in 2 of 29 H. pylori-positive subjects (6.9%) and none in the 17 H. pylori-negative (0%). Saliva PCR was positive in 4 of 14 H. pylori-positive subjects (28.6%) and none of 6 H. pylori-negative (0%)., Conclusion: The detection rates of H. pylori in DP and saliva by PCR were rather low, 6.9% and 28.6%, respectively, and these rates might have been underestimated by low sensitivity of the PCR method used in this study. However, the results that H. pylori was found in the DP and saliva suggest that the oral cavity can perform a role as a reservoir of H. pylori in Korea.
- Published
- 2000
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- View/download PDF
41. Avian models of inherited retinal disease.
- Author
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Semple-Rowland SL and Lee NR
- Subjects
- Animals, Chickens, Retina anatomy & histology, Disease Models, Animal, Retinal Diseases genetics
- Published
- 2000
- Full Text
- View/download PDF
42. Staged surgical treatment of obstructive sleep apnea syndrome: a review of 35 patients.
- Author
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Lee NR, Givens CD Jr, Wilson J, and Robins RB
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Polysomnography, Prospective Studies, Sleep Apnea Syndromes diagnosis, Surgical Procedures, Operative statistics & numerical data, Treatment Outcome, Sleep Apnea Syndromes surgery, Surgical Procedures, Operative methods
- Abstract
Purpose: The purpose of this study was to investigate the success of a staged surgical reconstruction of the upper airway for treatment of obstructive sleep apnea syndrome., Patients and Methods: Thirty-five patients with obstructive sleep apnea syndrome documented by nocturnal polysomnography were treated surgically with a staged protocol for reconstruction of the upper airway. All patients were evaluated preoperatively by a history and physical examination, including fiberoptic nasopharyngoscopy, oropharyngoscopy, and hypopharyngoscopy; cephalometric analysis; and laboratory polysomnography. All patients included were diagnosed with type II obstruction, with collapse at the oropharyngeal and hypopharyngeal levels. Stage I reconstruction consisted of uvulopalatopharyngoplasty (UPPP) by the Fujita method and anterior mandibular osteotomy (AMO) or inferior sagittal osteotomy (ISO) with genioglossus muscle advancement. If stage I was unsuccessful, patients were advanced to stage II and stage III, if necessary. Stage II reconstruction consisted of bimaxillary advancement with rigid fixation. Stage III reconstruction consisted of hyoid myotomy and advancement., Results: All patients underwent follow-up nocturnal polysomnography 4 to 6 months after the last surgical procedure. Most patients responded positively to stage I reconstruction (respiratory disturbance index [RDI] < 20, with O2 saturation 95+%). Twenty-four patients (69%) had postoperative RDIs of 20 or less. Of these, 11 patients (31%) had an RDI of five or fewer; seven patients (20%) had an RDI between 6 and 10, and six patients (17%) had an RDI between 10 and 20. The mean preoperative RDI was 53, and the mean postoperative RDI was 19. Of the three patients who elected to proceed to stage II reconstruction, all had a postoperative RDI of 10 or less (two patients [67%] had an RDI of 5 or less, and one patient [33%] had an RDI of 6 to 10)., Conclusion: This study showed that properly selected patients with obstructive sleep apnea syndrome benefit from a staged reconstruction of the upper airway.
- Published
- 1999
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43. A null mutation in the photoreceptor guanylate cyclase gene causes the retinal degeneration chicken phenotype.
- Author
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Semple-Rowland SL, Lee NR, Van Hooser JP, Palczewski K, and Baehr W
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Blindness enzymology, Blindness genetics, Calcium-Binding Proteins physiology, Chickens, Cloning, Molecular, Cyclic GMP metabolism, Disease Models, Animal, Down-Regulation, Gene Rearrangement, Guanylate Cyclase chemistry, Guanylate Cyclase-Activating Proteins, Humans, Molecular Sequence Data, Optic Atrophies, Hereditary enzymology, Optic Atrophies, Hereditary genetics, Phenotype, Photoreceptor Cells metabolism, Receptors, Cell Surface chemistry, Vision, Ocular genetics, Calcium-Binding Proteins genetics, Frameshift Mutation, Guanylate Cyclase genetics, Receptors, Cell Surface genetics, Retinal Degeneration enzymology, Retinal Degeneration genetics
- Abstract
The retinas of the retinal degeneration (rd) chicken are fully developed and possess normal morphology at hatching but fail to respond to light stimulation. Analyses of retinal cGMP, the internal messenger of phototransduction, show that the amount of cGMP in predegenerate, fully developed rd/rd photoreceptors is 5-10 times less than that seen in normal photoreceptor cells. We show that the low levels of cGMP in rd chicken retina are a consequence of a null mutation in the photoreceptor guanylate cyclase (GC1) gene. Thus, the rd chicken is a model for human Leber's congenital amaurosis. Absence of GC1 in rd retina prevents phototransduction and affects survival of rods and cones but does not interfere with normal photoreceptor development.
- Published
- 1998
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44. Enhancing mammography referral in primary care.
- Author
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Grady KE, Lemkau JP, Lee NR, and Caddell C
- Subjects
- Female, Humans, Male, Medical Audit, Middle Aged, Prospective Studies, Family Practice standards, Mammography statistics & numerical data, Patient Compliance, Patient Education as Topic standards, Primary Health Care standards, Referral and Consultation standards, Reminder Systems standards, Reward
- Abstract
Background: This 1-year randomized trial tested the efficacy of behavioral techniques for increasing mammography referrals by primary care physicians in small, community practices., Methods: Sixty-one practices were randomly assigned to one of three conditions: (1) education-only control, (2) education plus cue enhancement using mammography chart stickers, and (3) education plus cue enhancement plus feedback and token rewards. Quarterly chart audits of a defined sample (N = 11,716) of women patients 50 years of age or older were conducted to document mammography referrals, completions, and compliance., Results: Referral and completion rates increased from baseline to first quarter and gradually declined thereafter. Overall, these rates were higher in the cuing conditions than in the control condition. In contrast, compliance rates in both experimental conditions increased over the year while remaining static in the control condition, demonstrating a strong and continuing effect for cue enhancement. Compliance increases were greatest for physicians who were older, nonwhite, with a second speciality, in solo practice, not members of the AMA, not residency trained, and not board certified., Conclusions: Chart stickers can significantly increase mammography utilization in small, community practices. These practices are an efficient route to reaching large numbers of older women in need of mammography screening.
- Published
- 1997
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- View/download PDF
45. Treatment of obstructive sleep apnea syndrome. A review of surgical approaches.
- Author
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Givens CD Jr, Lee NR, and Wilson J
- Subjects
- Airway Obstruction, Humans, Hyoid Bone surgery, Mandible surgery, Maxilla surgery, Palate, Soft surgery, Pharynx surgery, Tracheostomy methods, Uvula surgery, Sleep Apnea Syndromes rehabilitation
- Published
- 1996
46. Physical structure and expression of alkBA encoding alkane hydroxylase and rubredoxin reductase from Pseudomonas maltophilia.
- Author
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Lee NR, Hwang MO, Jung GH, Kim YS, and Min KH
- Subjects
- Amino Acid Sequence, Cytochrome P-450 CYP4A, Cytochrome P-450 Enzyme System chemistry, Cytochrome P-450 Enzyme System metabolism, Escherichia coli enzymology, Gene Expression, Genetic Complementation Test, Kinetics, Mixed Function Oxygenases chemistry, Mixed Function Oxygenases metabolism, Molecular Sequence Data, NADH, NADPH Oxidoreductases chemistry, NADH, NADPH Oxidoreductases metabolism, Restriction Mapping, Sequence Homology, Amino Acid, Cytochrome P-450 Enzyme System biosynthesis, Genes, Bacterial, Mixed Function Oxygenases biosynthesis, NADH, NADPH Oxidoreductases biosynthesis, Pseudomonas enzymology, Pseudomonas genetics
- Abstract
The structural genes of the Pseudomonas maltophilia alk system, which are localized on the OCT plasmid were cloned as a 4.2-kilobase pair Hind III fragment. This fragment contains sequences for alkane hydroxylase gene (alkB) and rubredoxin reductase gene (alkA), respectively. The alkB gene encodes a 373-amino acid polypeptide (47.4 kD) that can be expressed at high levels in Pseudomonas and Escherichia coli. The alkBA genes were complemented with alkane hydroxylation in both bacteria. This result shows that alkBA gene is essential for alkane hydroxylation since chromosomal loci have been encoded for other enzymes involved in fatty acid oxidation.
- Published
- 1996
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47. Properties of clock-controlled and constitutive N-acetyltransferases from chick pineal cells.
- Author
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Wolfe MS, Lee NR, and Zatz M
- Subjects
- Ammonium Sulfate pharmacology, Animals, Chick Embryo, Kinetics, Melatonin, Pineal Gland physiology, Tryptamines pharmacology, Acetyl Coenzyme A physiology, Arylamine N-Acetyltransferase physiology, Circadian Rhythm physiology, Pineal Gland enzymology
- Abstract
The pineal gland synthesizes its hormone melatonin (O-methyl-N-acetylserotonin) from serotonin. Acetyl-CoA: serotonin N-acetyltransferase (SNAT), the enzyme that catalyzes the committed step in this biosynthesis, is largely restricted to the pineal gland and is regulated by adrenergic and circadian mechanisms. Another enzyme, acetyl-CoA: arylamine N-acetyltransferase (ANAT), having an apparently similar activity, is also present in the pineal. This enzyme, however, is not rhythmically regulated. SNAT activity of cultured chick pineal cells was obtained without ANAT after ammonium sulfate precipitation. ANAT activity was retained without SNAT activity after pre-incubation at 37 degrees C. Thus, each enzyme could be examined independently. Overlap in substrate specificity between the two enzymes was minimal. Kinetic analysis of the separated enzyme activities revealed that while SNAT operates via a random or ordered bi bi mechanism, ANAT catalysis occurs through a ping pong bi bi mechanism with substrate inhibition by acetyl-CoA. By size-exclusion chromatography, ANAT was confirmed to be 30-35 kDa, and SNAT was estimated at 15-20 kDa. Taken together, these results indicate that the two enzymes differ in their structure, reactivity, stability, and mechanism of catalysis.
- Published
- 1995
- Full Text
- View/download PDF
48. The impact of Hurricane Hugo and the San Francisco earthquake on a sample of people with rheumatoid arthritis.
- Author
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Grady KE, Reisine ST, Fifield J, Lee NR, McVay J, and Kelsey ME
- Subjects
- Adult, Female, Humans, Male, Middle Aged, San Francisco, South Carolina, Arthritis, Rheumatoid psychology, Disasters, Health Status, Stress, Psychological psychology
- Abstract
The health effects of two natural disasters on 32 people with rheumatoid arthritis (RA) were assessed during the second-year wave of interviews in an ongoing 3-year study. Although the severity of Hurricane Hugo exceeded that of the San Francisco earthquake, no significant differences in health impacts were found. Both groups reported significantly increased ratings of RA activity, pain, and depression compared with ratings during the first year. However, comparison with the rest of the sample (n = 767) showed that increases in disease activity and pain were a general phenomenon but that the increase in depression was unique to the disaster subsample. Physician health status assessments also indicated that those who experienced the disaster were more likely to be classified in later stages of the disease subsequent to the disaster and were more likely to experience flares. These results suggest that people with RA may constitute a special high-risk population for adverse health effects after natural disasters.
- Published
- 1991
- Full Text
- View/download PDF
49. Evaluation of rebreathing in various modifications of the Mapleson-D system.
- Author
-
Campbell RL, Lee NR, Shamaskin RG, Priest JH, and Rah KH
- Subjects
- Anesthesia, Dental instrumentation, Anesthesia, Inhalation instrumentation, Carbon Dioxide blood, Equipment Design, Humans, Oxygen, Tidal Volume, Anesthesia, Dental methods, Anesthesia, Inhalation methods, Carbon Dioxide metabolism, Nitrous Oxide, Respiration
- Abstract
Several modifications of the Bain system for nitrous oxide analgesia or general anesthesia were tested for rebreathing and retention of CO2. The classic Bain circuit causes the most rebreathing as measured by the fractional concentration of CO2 in a sample of inspired gas (FICO2), but stimulation of the respiratory system seems to allow near normal end tidal CO2 and arterial CO2 tensions. The most predictable systems that have the least amount of rebreathing are those that have the least dead space.
- Published
- 1985
- Full Text
- View/download PDF
50. Carbon dioxide absorption system with a simple modification of the Bain circuit.
- Author
-
Rah KH, Lee NR, McDougle ML, and Campbell RL
- Subjects
- Absorption, Anesthesia, Inhalation methods, Equipment Design, Anesthesia, Inhalation instrumentation, Carbon Dioxide
- Published
- 1982
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