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153. No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels

Author

Scott, Robert A., Chu, Audrey Yu-lei, Grarup, Niels, Manning, Alisa K., Hivert, Marie-France, Shungin, Dmitry, Tönjes, Anke, Yesupriya, Ajay, Barnes, Daniel, Bouatia-Naji, Nabila, Glazer, Nicole L., Jackson, Anne U., Kutalik, Zoltán, Lagou, Vasiliki, Marek, Diana, Rasmussen-Torvik, Laura J., Stringham, Heather M., Tanaka, Toshiko, Aadahl, Mette, Arking, Dan E., Bergmann, Sven, Boerwinkle, Eric, Bonnycastle, Lori L., Bornstein, Stefan R., Brunner, Eric, Bumpstead, Suzannah J., Brage, Soren, Carlson, Olga D., Chen, Han, Chen, Yii-Der Ida, Chines, Peter S., Collins, Francis S., Couper, David J., Dennison, Elaine M., Dowling, Nicole F., Egan, Josephine S., Ekelund, Ulf, Erdos, Michael R., Forouhi, Nita G., Fox, Caroline, Goodarzi, Mark O., Grässler, Jürgen, Gustafsson, Stefan, Hallmans, Göran, Hansen, Torben, Hingorani, Aroon, Holloway, John W., Hu, Frank B., Isomaa, Bo, Jameson, Karen A., Johansson, Ingegerd, Jonsson, Anna, Jørgensen, Torben, Kivimaki, Mika, Kovacs, Peter, Kumari, Meena, Kuusisto, Johanna, Laakso, Markku, Lecoeur, Cécile, Lévy-Marchal, Claire, Li, Guo, Loos, Ruth J.F., Lyssenko, Valeri, Marmot, Michael, Marques-Vidal, Pedro, Morken, Mario A., Müller, Gabriele, North, Kari E., Pankow, James S., Payne, Felicity, Prokopenko, Inga, Psaty, Bruce M., Renström, Frida, Rice, Ken, Rotter, Jerome I., Rybin, Denis, Sandholt, Camilla H., Sayer, Avan A., Shrader, Peter, Schwarz, Peter E.H., Siscovick, David S., Stančáková, Alena, Stumvoll, Michael, Teslovich, Tanya M., Waeber, Gérard, Williams, Gordon Harold, Witte, Daniel R., Wood, Andrew R., Xie, Weijia, Boehnke, Michael, Cooper, Cyrus, Ferrucci, Luigi, Froguel, Philippe, Groop, Leif, Kao, W.H. Linda, Vollenweider, Peter, Walker, Mark, Watanabe, Richard M., Pedersen, Oluf, Meigs, James Benjamin, Ingelsson, Erik, Barroso, Inês, Florez, Jose Carlos, Franks, Paul W., Dupuis, Josée, Wareham, Nicholas J., and Langenberg, Claudia

Abstract

Gene–lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13–0.31], P = 1.63 × 10−6). All SNPs were associated with 2-h glucose (β = 0.06–0.12 mmol/allele, P ≤ 1.53 × 10−7), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene–lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

Published
2012
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154. Large-Scale Association Analysis Provides Insights into the Genetic Architecture and Pathophysiology of Type 2 Diabetes

Author

Morris, Andrew P, Voight, Benjamin F, Teslovich, Tanya M, Ferreira, Teresa, Segré, Ayellet V, Steinthorsdottir, Valgerdur, Strawbridge, Rona J, Khan, Hassan, Grallert, Harald, Mahajan, Anubha, Prokopenko, Inga, Kang, Hyun Min, Dina, Christian, Esko, Tonu, Fraser, Ross M, Kanoni, Stavroula, Kumar, Ashish, Lagou, Vasiliki, Langenberg, Claudia, Luan, Jian’an, Lindgren, Cecilia M, Müller-Nurasyid, Martina, Pechlivanis, Sonali, Rayner, N William, Scott, Laura J, Wiltshire, Steven, Yengo, Loic, Kinnunen, Leena, Rossin, Elizabeth J, Raychaudhuri, Soumya, Johnson, Andrew D, Dimas, Antigone S, Loos, Ruth J F, Vedantam, Sailaja, Chen, Han, Florez, Jose Carlos, Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Couper, David J, Kao, Wen Hong L, Li, Man, Cornelis, Marilyn, Kraft, Peter Elias, Sun, Qi, van Dam, Rob M, Stringham, Heather M, Chines, Peter S, Fischer, Krista, Fontanillas, Pierre, Holmen, Oddgeir L, Hunt, Sarah E, Jackson, Anne U, Kong, Augustine, Lawrence, Robert, Meyer, Julia, Perry, John R B, Platou, Carl G P, Potter, Simon, Rehnberg, Emil, Robertson, Neil, Sivapalaratnam, Suthesh, Stančáková, Alena, Stirrups, Kathleen, Thorleifsson, Gudmar, Tikkanen, Emmi, Wood, Andrew R, Almgren, Peter, Atalay, Mustafa, Benediktsson, Rafn, Bonnycastle, Lori L, Burtt, Noël, Carey, Jason, Charpentier, Guillaume, Crenshaw, Andrew T, Doney, Alex S F, Dorkhan, Mozhgan, Edkins, Sarah, Emilsson, Valur, Eury, Elodie, Forsen, Tom, Gertow, Karl, Gigante, Bruna, Grant, George B, Groves, Christopher J, Guiducci, Candace, Herder, Christian, Hreidarsson, Astradur B, Hui, Jennie, James, Alan, Jonsson, Anna, Rathmann, Wolfgang, Klopp, Norman, Kravic, Jasmina, Krjutškov, Kaarel, Langford, Cordelia, Leander, Karin, Lindholm, Eero, Lobbens, Stéphane, Männistö, Satu, Mirza, Ghazala, Mühleisen, Thomas W, Musk, Bill, Parkin, Melissa Ann, Rallidis, Loukianos, Saramies, Jouko, Sennblad, Bengt, Shah, Sonia, Sigurðsson, Gunnar, Silveira, Angela, Steinbach, Gerald, Thorand, Barbara, Trakalo, Joseph, Veglia, Fabrizio, Wennauer, Roman, Winckler, Wendy, Zabaneh, Delilah, Campbell, Harry, van Duijn, Cornelia, Uitterlinden, Andre G, Hofman, Albert, Sijbrands, Eric, Abecasis, Goncalo R, Owen, Katharine R, Zeggini, Eleftheria, Trip, Mieke D, Forouhi, Nita G, Syvänen, Ann-Christine, Eriksson, Johan G, Peltonen, Leena, Nöthen, Markus M, Balkau, Beverley, Palmer, Colin N A, Lyssenko, Valeriya, Tuomi, Tiinamaija, Isomaa, Bo, Hunter, David J., Qi, Lu, Shuldiner, Alan R, Roden, Michael, Barroso, Ines, Wilsgaard, Tom, Beilby, John, Hovingh, Kees, Price, Jackie F, Wilson, James F, Rauramaa, Rainer, Lakka, Timo A, Lind, Lars, Dedoussis, George, Njølstad, Inger, Pedersen, Nancy L, Khaw, Kay-Tee, Wareham, Nicholas J, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Korpi-Hyövälti, Eeva, Saltevo, Juha, Laakso, Markku, Kuusisto, Johanna, Metspalu, Andres, Collins, Francis S, Mohlke, Karen L, Bergman, Richard N, Tuomilehto, Jaakko, Boehm, Bernhard O, Gieger, Christian, Hveem, Kristian, Cauchi, Stephane, Froguel, Philippe, Baldassarre, Damiano, Tremoli, Elena, Humphries, Steve E, Saleheen, Danish, Danesh, John, Ingelsson, Erik, Ripatti, Samuli, Salomaa, Veikko, Erbel, Raimund, Jöckel, Karl-Heinz, Moebus, Susanne, Peters, Annette, Illig, Thomas, de Faire, Ulf, Hamsten, Anders, Morris, Andrew D, Donnelly, Peter J, Frayling, Timothy M, Hattersley, Andrew T, Boerwinkle, Eric, Melander, Olle, Kathiresan, Sekar, Nilsson, Peter M, Deloukas, Panos, Thorsteinsdottir, Unnur, Groop, Leif C, Stefansson, Kari, Hu, Frank B., Pankow, James S, Dupuis, Josée, Meigs, James Benjamin, Altshuler, David Matthew, Boehnke, Michael, and McCarthy, Mark I

Abstract

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis.

Published
2012
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155. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Author

Scott, Robert A, Lagou, Vasiliki, Welch, Ryan P, Wheeler, Eleanor, Montasser, May E, Luan, Jian’an, Mägi, Reedik, Strawbridge, Rona J, Rehnberg, Emil, Gustafsson, Stefan, Kanoni, Stavroula, Rasmussen-Torvik, Laura J, Yengo, Loïc, Lecoeur, Cecile, Shungin, Dmitry, Sanna, Serena, Sidore, Carlo, Johnson, Paul C D, Jukema, J Wouter, Johnson, Toby, Mahajan, Anubha, Verweij, Niek, Thorleifsson, Gudmar, Hottenga, Jouke-Jan, Shah, Sonia, Smith, Albert V, Sennblad, Bengt, Gieger, Christian, Salo, Perttu, Perola, Markus, Timpson, Nicholas J, Evans, David M, Pourcain, Beate St, Wu, Ying, Andrews, Jeanette S, Hui, Jennie, Bielak, Lawrence F, Zhao, Wei, Horikoshi, Momoko, Navarro, Pau, Isaacs, Aaron, O’Connell, Jeffrey R, Stirrups, Kathleen, Vitart, Veronique, Hayward, Caroline, Esko, Tönu, Mihailov, Evelin, Fraser, Ross M, Fall, Tove, Voight, Benjamin F, Raychaudhuri, Soumya, Chen, Han, Lindgren, Cecilia M, Morris, Andrew P, Rayner, Nigel W, Robertson, Neil, Rybin, Denis, Liu, Ching-Ti, Beckmann, Jacques S, Willems, Sara M, Chines, Peter S, Jackson, Anne U, Kang, Hyun Min, Stringham, Heather M, Song, Kijoung, Tanaka, Toshiko, Peden, John F, Goel, Anuj, Hicks, Andrew A, An, Ping, Müller-Nurasyid, Martina, Franco-Cereceda, Anders, Folkersen, Lasse, Marullo, Letizia, Jansen, Hanneke, Oldehinkel, Albertine J, Bruinenberg, Marcel, Pankow, James S, North, Kari E, Forouhi, Nita G, Loos, Ruth J F, Edkins, Sarah, Varga, Tibor V, Hallmans, Göran, Oksa, Heikki, Antonella, Mulas, Nagaraja, Ramaiah, Trompet, Stella, Ford, Ian, Bakker, Stephan J L, Kong, Augustine, Kumari, Meena, Gigante, Bruna, Herder, Christian, Munroe, Patricia B, Caulfield, Mark, Antti, Jula, Mangino, Massimo, Small, Kerrin, Miljkovic, Iva, Liu, Yongmei, Atalay, Mustafa, Kiess, Wieland, James, Alan L, Rivadeneira, Fernando, Uitterlinden, Andre G, Palmer, Colin N A, Doney, Alex S F, Willemsen, Gonneke, Smit, Johannes H, Campbell, Susan, Polasek, Ozren, Bonnycastle, Lori L, Hercberg, Serge, Dimitriou, Maria, Bolton, Jennifer L, Fowkes, Gerard R, Kovacs, Peter, Lindström, Jaana, Zemunik, Tatijana, Bandinelli, Stefania, Wild, Sarah H, Basart, Hanneke V, Rathmann, Wolfgang, Grallert, Harald, Maerz, Winfried, Kleber, Marcus E, Boehm, Bernhard O, Peters, Annette, Pramstaller, Peter P, Province, Michael A, Borecki, Ingrid B, Hastie, Nicholas D, Rudan, Igor, Campbell, Harry, Watkins, Hugh, Farrall, Martin, Stumvoll, Michael, Ferrucci, Luigi, Waterworth, Dawn M, Bergman, Richard N, Collins, Francis S, Tuomilehto, Jaakko, Watanabe, Richard M, de Geus, Eco J C, Penninx, Brenda W, Hofman, Albert, Oostra, Ben A, Psaty, Bruce M, Vollenweider, Peter, Wilson, James F, Wright, Alan F, Hovingh, G Kees, Metspalu, Andres, Uusitupa, Matti, Magnusson, Patrik K E, Kyvik, Kirsten O, Kaprio, Jaakko, Price, Jackie F, Dedoussis, George V, Deloukas, Panos, Meneton, Pierre, Lind, Lars, Boehnke, Michael, Shuldiner, Alan R, van Duijn, Cornelia M, Morris, Andrew D, Toenjes, Anke, Peyser, Patricia A, Beilby, John P, Körner, Antje, Kuusisto, Johanna, Laakso, Markku, Bornstein, Stefan R, Schwarz, Peter E H, Lakka, Timo A, Rauramaa, Rainer, Adair, Linda S, Smith, George Davey, Spector, Tim D, Illig, Thomas, de Faire, Ulf, Hamsten, Anders, Gudnason, Vilmundur, Kivimaki, Mika, Hingorani, Aroon, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Boomsma, Dorret I, Stefansson, Kari, van der Harst, Pim, Dupuis, Josée, Pedersen, Nancy L, Sattar, Naveed, Harris, Tamara B, Cucca, Francesco, Ripatti, Samuli, Salomaa, Veikko, Mohlke, Karen L, Balkau, Beverley, Froguel, Philippe, Pouta, Anneli, Jarvelin, Marjo-Riitta, Wareham, Nicholas J, Bouatia-Naji, Nabila, McCarthy, Mark I, Franks, Paul W, Meigs, James Benjamin, Teslovich, Tanya M, Florez, Jose Carlos, Langenberg, Claudia, Ingelsson, Erik, Prokopenko, Inga, and Barroso, Inês

Abstract

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control.

Published
2012
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156. Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant

Author

Kanoni, Stavroula, Nettleton, Jennifer A., Hivert, Marie-France, Ye, Zheng, van Rooij, Frank J.A., Shungin, Dmitry, Sonestedt, Emily, Ngwa, Julius S., Wojczynski, Mary K., Lemaitre, Rozenn N., Gustafsson, Stefan, Tanaka, Toshiko, Hindy, George, Saylor, Georgia, Renstrom, Frida, Bennett, Amanda J., van Duijn, Cornelia M., Hoogeveen, Ron C., Houston, Denise K., Jacques, Paul F., Johansson, Ingegerd, Lind, Lars, Liu, Yongmei, McKeown, Nicola, Ordovas, Jose, Pankow, James S., Sijbrands, Eric J.G., Syvänen, Ann-Christine, Uitterlinden, André G., Yannakoulia, Mary, Zillikens, M. Carola, Wareham, Nick J., Prokopenko, Inga, Bandinelli, Stefania, Forouhi, Nita G., Cupples, L. Adrienne, Loos, Ruth J., Hallmans, Goran, Dupuis, Josée, Langenberg, Claudia, Ferrucci, Luigi, Kritchevsky, Stephen B., McCarthy, Mark I., Ingelsson, Erik, Borecki, Ingrid B., Witteman, Jacqueline C.M., Orho-Melander, Marju, Siscovick, David S., Franks, Paul W., Dedoussis, George V., Anderson, Jennifer S., Florez, Jose Carlos, Fox, Caroline, Hofman, Albert, Hu, Frank B., and Meigs, James Benjamin

Abstract

Objective: Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. Research Design and Methods: We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes. Results: We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: −0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: −0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant. Conclusions: Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.

Published
2011
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157. Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

Author

Lindgren, Cecilia M., Heid, Iris M., Randall, Joshua C., Lamina, Claudia, Steinthorsdottir, Valgerdur, Speliotes, Elizabeth K., Thorleifsson, Gudmar, Willer, Cristen J., Herrera, Blanca M., Jackson, Anne U., Lim, Noha, Scheet, Paul, Soranzo, Nicole, Amin, Najaf, Aulchenko, Yurii S., Chambers, John C., Drong, Alexander, Luan, Jian'an, Rivadeneira, Fernando, Sanna, Serena, Timpson, Nicholas J., Zillikens, M. Carola, Almgren, Peter, Bandinelli, Stefania, Bennett, Amanda J., Bergman, Richard N., Bonnycastle, Lori L., Bumpstead, Suzannah J., Chanock, Stephen J., Cherkas, Lynn, Chines, Peter, Coin, Lachlan, Cooper, Cyrus, Crawford, Gabriel, Doering, Angela, Dominiczak, Anna, Doney, Alex S. F., Ebrahim, Shah, Elliott, Paul, Erdos, Michael R., Estrada, Karol, Ferrucci, Luigi, Fischer, Guido, Forouhi, Nita G., Gieger, Christian, Grallert, Harald, Groves, Christopher J., Grundy, Scott, Guiducci, Candace, Hadley, David, Hamsten, Anders, Havulinna, Aki S., Holle, Rolf, Holloway, John W., Illig, Thomas, Isomaa, Bo, Jacobs, Leonie C., Jameson, Karen, Jousilahti, Pekka, Karpe, Fredrik, Kuusisto, Johanna, Laitinen, Jaana, Lathrop, G. Mark, Lawlor, Debbie A., Mangino, Massimo, McArdle, Wendy L., Meitinger, Thomas, Morken, Mario A., Morris, Andrew P., Munroe, Patricia, Narisu, Narisu, Nordström, Anna, Nordström, Peter, Oostra, Ben A., Palmer, Colin N. A., Payne, Felicity, Peden, John F., Prokopenko, Inga, Renström, Frida, Ruokonen, Aimo, Salomaa, Veikko, Sandhu, Manjinder S., Scuteri, Angelo, Silander, Kaisa, Song, Kijoung, Stringham, Heather M., Swift, Amy J., Tuomi, Tiinamaija, Uda, Manuela, Vollenweider, Peter, Waeber, Gerard, Wallace, Chris, Walters, G. Bragi, Weedon, Michael N., Witteman, Jacqueline C. M., Zhang, Cuilin, Zhang, Weihua, Caulfield, Mark J., Collins, Francis S., Davey Smith, George, Day, Ian N. M., Franks, Paul W., Hattersley, Andrew T., Jarvelin, Marjo-Riitta, Kong, Augustine, Kooner, Jaspal S., Laakso, Markku, Lakatta, Edward, Mooser, Vincent, Morris, Andrew D., Peltonen, Leena, Samani, Nilesh J., Spector, Timothy D., Strachan, David P., Tanaka, Toshiko, Tuomilehto, Jaakko, Uitterlinden, André G., van Duijn, Cornelia M., Wareham, Nicholas J., Waterworth, Dawn M., Boehnke, Michael, Deloukas, Panos, Groop, Leif, Thorsteinsdottir, Unnur, Schlessinger, David, Wichmann, H.-Erich, Frayling, Timothy M., Abecasis, Gonçalo R., Loos, Ruth J. F., Stefansson, Kari, Mohlke, Karen L., Barroso, Inês, Hirschhorn, Joel Naom, McCarthy, Mark I., Watkins, Hugh, The Wellcome Trust Case Control Consortium, Hunter, David J., Hu, Frank B., Yuan, Xin, Scott, Laura J., Hofman, Albert, Zhao, Jing Hua, Lyon, Helen N, and Qi, Lu

Subjects
diabetes and endocrinology, obesity, type 2 diabetes, complex traits, genetics and genomics
Abstract

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist–hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×\(10^{-11}\)) and MSRA (WC, P = 8.9×\(10^{-9}\)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×\(10^{-8}\)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

Published
2009
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158. A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

Author

Fumiaki Imamura, Stephen J Sharp, Albert Koulman, Matthias B Schulze, Janine Kröger, Julian L Griffin, José M Huerta, Marcela Guevara, Ivonne Sluijs, Antonio Agudo, Eva Ardanaz, Beverley Balkau, Heiner Boeing, Veronique Chajes, Christina C Dahm, Courtney Dow, Guy Fagherazzi, Edith J M Feskens, Paul W Franks, Diana Gavrila, Marc Gunter, Rudolf Kaaks, Timothy J Key, Kay-Tee Khaw, Tilman Kühn, Olle Melander, Elena Molina-Portillo, Peter M Nilsson, Anja Olsen, Kim Overvad, Domenico Palli, Salvatore Panico, Olov Rolandsson, Sabina Sieri, Carlotta Sacerdote, Nadia Slimani, Annemieke M W Spijkerman, Anne Tjønneland, Rosario Tumino, Yvonne T van der Schouw, Claudia Langenberg, Elio Riboli, Nita G Forouhi, and Nick J Wareham

Subjects
Medicine
Abstract

BackgroundCombinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated.Methods and findingsWe measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding.ConclusionsA combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.

Published
2017
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159. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions.

Author

Dmitry Shungin, Wei Q Deng, Tibor V Varga, Jian'an Luan, Evelin Mihailov, Andres Metspalu, GIANT Consortium, Andrew P Morris, Nita G Forouhi, Cecilia Lindgren, Patrik K E Magnusson, Nancy L Pedersen, Göran Hallmans, Audrey Y Chu, Anne E Justice, Mariaelisa Graff, Thomas W Winkler, Lynda M Rose, Claudia Langenberg, L Adrienne Cupples, Paul M Ridker, Nicholas J Wareham, Ken K Ong, Ruth J F Loos, Daniel I Chasman, Erik Ingelsson, Tuomas O Kilpeläinen, Robert A Scott, Reedik Mägi, Guillaume Paré, and Paul W Franks

Subjects
Genetics, QH426-470
Abstract

Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pv and Pm were stronger for SNPs with established marginal effects (Spearman's ρ = 0.401 for triglycerides, and ρ = 0.236 for BMI) compared to all SNPs. When Pv and Pm were compared for all pruned SNPs, only BMI was statistically significant (Spearman's ρ = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the Pv distribution (Pbinomial

Published
2017
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160. Impact of a Dedicated Research Rotation during Ophthalmology Residency

Author

Nita G. Valikodath, Blake V. Fausett, Gale A. Oren, Katherine Whitney, Maria A. Woodward, and Shahzad I. Mian

Subjects
research rotation, scholarly activity, residency training, medical education, Ophthalmology, RE1-994
Abstract

Abstract Background The Accreditation Council for Graduate Medical Education (ACGME) requires that ophthalmology residents participate in scholarly activity during residency. However, residents lack protected time for research. Objective This article aims to determine the impact of a dedicated research rotation on scholarly productivity and research experience during residency. Methods This cohort study compared two groups of ophthalmology residents. Residents who graduated between 2004 and 2009 did not have dedicated research time and served as control residents (CR), while residents who graduated between 2010 and 2015 had a dedicated research rotation and served as the intervention group (research residents, RR). Primary outcomes included publications and presentations recorded over a 4-year period, spanning the 3 years of residency and the first year after graduation. These were analyzed by linear regression and t-tests. Residents also took surveys regarding research experience and chi-squared tests and logistic regression were used to compare these results. Results The RR had 0.97 more publications and 1.3 more presentations compared with the CR after adjusting for PhD status, pre-residency publications and presentations, age at graduation, gender, and race (p = 0.09 and p = 0.02, respectively). RR had higher odds of reporting adequate time to complete research (odds ratio [OR] = 13.11, 95% confidence interval [CI]: 3.58–48.03, p

Published
2017
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161. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

Author

Luca A Lotta, Robert A Scott, Stephen J Sharp, Stephen Burgess, Jian'an Luan, Therese Tillin, Amand F Schmidt, Fumiaki Imamura, Isobel D Stewart, John R B Perry, Luke Marney, Albert Koulman, Edward D Karoly, Nita G Forouhi, Rasmus J O Sjögren, Erik Näslund, Juleen R Zierath, Anna Krook, David B Savage, Julian L Griffin, Nishi Chaturvedi, Aroon D Hingorani, Kay-Tee Khaw, Inês Barroso, Mark I McCarthy, Stephen O'Rahilly, Nicholas J Wareham, and Claudia Langenberg

Subjects
Medicine
Abstract

BackgroundHigher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question.Methods and findingsGenome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8). The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25), encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes.ConclusionsEvidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes.

Published
2016
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173. Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.

Author

Nita G Forouhi, Fumiaki Imamura, Stephen J Sharp, Albert Koulman, Matthias B Schulze, Jusheng Zheng, Zheng Ye, Ivonne Sluijs, Marcela Guevara, José María Huerta, Janine Kröger, Laura Yun Wang, Keith Summerhill, Julian L Griffin, Edith J M Feskens, Aurélie Affret, Pilar Amiano, Heiner Boeing, Courtney Dow, Guy Fagherazzi, Paul W Franks, Carlos Gonzalez, Rudolf Kaaks, Timothy J Key, Kay Tee Khaw, Tilman Kühn, Lotte Maxild Mortensen, Peter M Nilsson, Kim Overvad, Valeria Pala, Domenico Palli, Salvatore Panico, J Ramón Quirós, Miguel Rodriguez-Barranco, Olov Rolandsson, Carlotta Sacerdote, Augustin Scalbert, Nadia Slimani, Annemieke M W Spijkerman, Anne Tjonneland, Maria-Jose Tormo, Rosario Tumino, Daphne L van der A, Yvonne T van der Schouw, Claudia Langenberg, Elio Riboli, and Nicholas J Wareham

Subjects
Medicine
Abstract

BackgroundWhether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.Methods and findingsPlasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs.ConclusionsThese large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.

Published
2016
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174. Dietary Diversity, Diet Cost, and Incidence of Type 2 Diabetes in the United Kingdom: A Prospective Cohort Study.

Author

Annalijn I Conklin, Pablo Monsivais, Kay-Tee Khaw, Nicholas J Wareham, and Nita G Forouhi

Subjects
Medicine
Abstract

BackgroundDiet is a key modifiable risk factor for multiple chronic conditions, including type 2 diabetes (T2D). Consuming a range of foods from the five major food groups is advocated as critical to healthy eating, but the association of diversity across major food groups with T2D is not clear and the relationship of within-food-group diversity is unknown. In addition, there is a growing price gap between more and less healthy foods, which may limit the uptake of varied diets. The current study had two aims: first, to examine the association of reported diversity of intake of food groups as well as their subtypes with risk of developing T2D, and second, to estimate the monetary cost associated with dietary diversity.Methods and findingsA prospective study of 23,238 participants in the population-based EPIC-Norfolk cohort completed a baseline Food Frequency Questionnaire in 1993-1997 and were followed up for a median of 10 y. We derived a total diet diversity score and additional scores for diversity within each food group (dairy products, fruits, vegetables, meat and alternatives, and grains). We used multivariable Cox regression analyses for incident diabetes (892 new cases), and multivariable linear regression for diet cost. Greater total diet diversity was associated with 30% lower risk of developing T2D (Hazard ratio [HR] 0.70 [95% CI 0.51 to 0.95]) comparing diets comprising all five food groups to those with three or fewer, adjusting for confounders including obesity and socioeconomic status. In analyses of diversity within each food group, greater diversity in dairy products (HR 0.61 [0.45 to 0.81]), fruits (HR 0.69 [0.52 to 0.90]), and vegetables (HR 0.67 [0.52 to 0.87]) were each associated with lower incident diabetes. The cost of consuming a diet covering all 5 food groups was 18% higher (£4.15/day [4.14 to 4.16]) than one comprising three or fewer groups. Key limitations are the self-reported dietary data and the binary scoring approach whereby some food groups contained both healthy and less healthy food items.ConclusionsA diet characterized by regular consumption of all five food groups and by greater variety of dairy, fruit, and vegetable subtypes, appears important for a reduced risk of diabetes. However, such a diet is more expensive. Public health efforts to prevent diabetes should include food price policies to promote healthier, more varied diets.

Published
2016
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175. Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Author

Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, Yingchang Lu, Reedik Mägi, Evelin Mihailov, Tune H Pers, Sina Rüeger, Alexander Teumer, Georg B Ehret, Teresa Ferreira, Nancy L Heard-Costa, Juha Karjalainen, Vasiliki Lagou, Anubha Mahajan, Michael D Neinast, Inga Prokopenko, Jeannette Simino, Tanya M Teslovich, Rick Jansen, Harm-Jan Westra, Charles C White, Devin Absher, Tarunveer S Ahluwalia, Shafqat Ahmad, Eva Albrecht, Alexessander Couto Alves, Jennifer L Bragg-Gresham, Anton J M de Craen, Joshua C Bis, Amélie Bonnefond, Gabrielle Boucher, Gemma Cadby, Yu-Ching Cheng, Charleston W K Chiang, Graciela Delgado, Ayse Demirkan, Nicole Dueker, Niina Eklund, Gudny Eiriksdottir, Joel Eriksson, Bjarke Feenstra, Krista Fischer, Francesca Frau, Tessel E Galesloot, Frank Geller, Anuj Goel, Mathias Gorski, Tanja B Grammer, Stefan Gustafsson, Saskia Haitjema, Jouke-Jan Hottenga, Jennifer E Huffman, Anne U Jackson, Kevin B Jacobs, Åsa Johansson, Marika Kaakinen, Marcus E Kleber, Jari Lahti, Irene Mateo Leach, Benjamin Lehne, Youfang Liu, Ken Sin Lo, Mattias Lorentzon, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Barbara McKnight, Carolina Medina-Gomez, Keri L Monda, May E Montasser, Gabriele Müller, Martina Müller-Nurasyid, Ilja M Nolte, Kalliope Panoutsopoulou, Laura Pascoe, Lavinia Paternoster, Nigel W Rayner, Frida Renström, Federica Rizzi, Lynda M Rose, Kathy A Ryan, Perttu Salo, Serena Sanna, Hubert Scharnagl, Jianxin Shi, Albert Vernon Smith, Lorraine Southam, Alena Stančáková, Valgerdur Steinthorsdottir, Rona J Strawbridge, Yun Ju Sung, Ioanna Tachmazidou, Toshiko Tanaka, Gudmar Thorleifsson, Stella Trompet, Natalia Pervjakova, Jonathan P Tyrer, Liesbeth Vandenput, Sander W van der Laan, Nathalie van der Velde, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Efthymia Vlachopoulou, Lindsay L Waite, Sophie R Wang, Zhaoming Wang, Sarah H Wild, Christina Willenborg, James F Wilson, Andrew Wong, Jian Yang, Loïc Yengo, Laura M Yerges-Armstrong, Lei Yu, Weihua Zhang, Jing Hua Zhao, Ehm A Andersson, Stephan J L Bakker, Damiano Baldassarre, Karina Banasik, Matteo Barcella, Cristina Barlassina, Claire Bellis, Paola Benaglio, John Blangero, Matthias Blüher, Fabrice Bonnet, Lori L Bonnycastle, Heather A Boyd, Marcel Bruinenberg, Aron S Buchman, Harry Campbell, Yii-Der Ida Chen, Peter S Chines, Simone Claudi-Boehm, John Cole, Francis S Collins, Eco J C de Geus, Lisette C P G M de Groot, Maria Dimitriou, Jubao Duan, Stefan Enroth, Elodie Eury, Aliki-Eleni Farmaki, Nita G Forouhi, Nele Friedrich, Pablo V Gejman, Bruna Gigante, Nicola Glorioso, Alan S Go, Omri Gottesman, Jürgen Gräßler, Harald Grallert, Niels Grarup, Yu-Mei Gu, Linda Broer, Annelies C Ham, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew T Hattersley, Andrew C Heath, Anjali K Henders, Dena Hernandez, Hans Hillege, Oddgeir Holmen, Kees G Hovingh, Jennie Hui, Lise L Husemoen, Nina Hutri-Kähönen, Pirro G Hysi, Thomas Illig, Philip L De Jager, Shapour Jalilzadeh, Torben Jørgensen, J Wouter Jukema, Markus Juonala, Stavroula Kanoni, Maria Karaleftheri, Kay Tee Khaw, Leena Kinnunen, Steven J Kittner, Wolfgang Koenig, Ivana Kolcic, Peter Kovacs, Nikolaj T Krarup, Wolfgang Kratzer, Janine Krüger, Diana Kuh, Meena Kumari, Theodosios Kyriakou, Claudia Langenberg, Lars Lannfelt, Chiara Lanzani, Vaneet Lotay, Lenore J Launer, Karin Leander, Jaana Lindström, Allan Linneberg, Yan-Ping Liu, Stéphane Lobbens, Robert Luben, Valeriya Lyssenko, Satu Männistö, Patrik K Magnusson, Wendy L McArdle, Cristina Menni, Sigrun Merger, Lili Milani, Grant W Montgomery, Andrew P Morris, Narisu Narisu, Mari Nelis, Ken K Ong, Aarno Palotie, Louis Pérusse, Irene Pichler, Maria G Pilia, Anneli Pouta, Myriam Rheinberger, Rasmus Ribel-Madsen, Marcus Richards, Kenneth M Rice, Treva K Rice, Carlo Rivolta, Veikko Salomaa, Alan R Sanders, Mark A Sarzynski, Salome Scholtens, Robert A Scott, William R Scott, Sylvain Sebert, Sebanti Sengupta, Bengt Sennblad, Thomas Seufferlein, Angela Silveira, P Eline Slagboom, Jan H Smit, Thomas H Sparsø, Kathleen Stirrups, Ronald P Stolk, Heather M Stringham, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Emmanouil Tsafantakis, Peter J van der Most, Uwe Völker, Marie-Claude Vohl, Judith M Vonk, Melanie Waldenberger, Ryan W Walker, Roman Wennauer, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Alan F Wright, M Carola Zillikens, Suzanne C van Dijk, Natasja M van Schoor, Folkert W Asselbergs, Paul I W de Bakker, Jacques S Beckmann, John Beilby, David A Bennett, Richard N Bergman, Sven Bergmann, Carsten A Böger, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, John C Chambers, Stephen J Chanock, Daniel I Chasman, Francesco Cucca, Daniele Cusi, George Dedoussis, Jeanette Erdmann, Johan G Eriksson, Denis A Evans, Ulf de Faire, Martin Farrall, Luigi Ferrucci, Ian Ford, Lude Franke, Paul W Franks, Philippe Froguel, Ron T Gansevoort, Christian Gieger, Henrik Grönberg, Vilmundur Gudnason, Ulf Gyllensten, Per Hall, Anders Hamsten, Pim van der Harst, Caroline Hayward, Markku Heliövaara, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Frank Hu, Heikki V Huikuri, Kristian Hveem, Alan L James, Joanne M Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Sekar Kathiresan, Lambertus A L M Kiemeney, Mika Kivimaki, Paul B Knekt, Heikki A Koistinen, Jaspal S Kooner, Seppo Koskinen, Johanna Kuusisto, Winfried Maerz, Nicholas G Martin, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Guillaume Lettre, Douglas F Levinson, Lars Lind, Marja-Liisa Lokki, Pekka Mäntyselkä, Mads Melbye, Andres Metspalu, Braxton D Mitchell, Frans L Moll, Jeffrey C Murray, Arthur W Musk, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Ben A Oostra, Lyle J Palmer, James S Pankow, Gerard Pasterkamp, Nancy L Pedersen, Oluf Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P Pramstaller, Bruce M Psaty, Lu Qi, Thomas Quertermous, Olli T Raitakari, Tuomo Rankinen, Rainer Rauramaa, Paul M Ridker, John D Rioux, Fernando Rivadeneira, Jerome I Rotter, Igor Rudan, Hester M den Ruijter, Juha Saltevo, Naveed Sattar, Heribert Schunkert, Peter E H Schwarz, Alan R Shuldiner, Juha Sinisalo, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Jan A Staessen, Bandinelli Stefania, Unnur Thorsteinsdottir, Michael Stumvoll, Jean-Claude Tardif, Elena Tremoli, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, André L M Verbeek, Sita H Vermeulen, Jorma S Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Gérard Waeber, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, Eleftheria Zeggini, arcOGEN Consortium, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Aravinda Chakravarti, Deborah J Clegg, L Adrienne Cupples, Penny Gordon-Larsen, Cashell E Jaquish, D C Rao, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Sonja I Berndt, Michael Boehnke, Panos Deloukas, Caroline S Fox, Leif C Groop, David J Hunter, Erik Ingelsson, Robert C Kaplan, Mark I McCarthy, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Joel N Hirschhorn, Cecilia M Lindgren, Iris M Heid, Kari E North, Ingrid B Borecki, Zoltán Kutalik, and Ruth J F Loos

Subjects
Genetics, QH426-470
Abstract

[This corrects the article DOI: 10.1371/journal.pgen.1005378.].

Published
2016
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176. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Author

Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, Yingchang Lu, Reedik Mägi, Evelin Mihailov, Tune H Pers, Sina Rüeger, Alexander Teumer, Georg B Ehret, Teresa Ferreira, Nancy L Heard-Costa, Juha Karjalainen, Vasiliki Lagou, Anubha Mahajan, Michael D Neinast, Inga Prokopenko, Jeannette Simino, Tanya M Teslovich, Rick Jansen, Harm-Jan Westra, Charles C White, Devin Absher, Tarunveer S Ahluwalia, Shafqat Ahmad, Eva Albrecht, Alexessander Couto Alves, Jennifer L Bragg-Gresham, Anton J M de Craen, Joshua C Bis, Amélie Bonnefond, Gabrielle Boucher, Gemma Cadby, Yu-Ching Cheng, Charleston W K Chiang, Graciela Delgado, Ayse Demirkan, Nicole Dueker, Niina Eklund, Gudny Eiriksdottir, Joel Eriksson, Bjarke Feenstra, Krista Fischer, Francesca Frau, Tessel E Galesloot, Frank Geller, Anuj Goel, Mathias Gorski, Tanja B Grammer, Stefan Gustafsson, Saskia Haitjema, Jouke-Jan Hottenga, Jennifer E Huffman, Anne U Jackson, Kevin B Jacobs, Åsa Johansson, Marika Kaakinen, Marcus E Kleber, Jari Lahti, Irene Mateo Leach, Benjamin Lehne, Youfang Liu, Ken Sin Lo, Mattias Lorentzon, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Barbara McKnight, Carolina Medina-Gomez, Keri L Monda, May E Montasser, Gabriele Müller, Martina Müller-Nurasyid, Ilja M Nolte, Kalliope Panoutsopoulou, Laura Pascoe, Lavinia Paternoster, Nigel W Rayner, Frida Renström, Federica Rizzi, Lynda M Rose, Kathy A Ryan, Perttu Salo, Serena Sanna, Hubert Scharnagl, Jianxin Shi, Albert Vernon Smith, Lorraine Southam, Alena Stančáková, Valgerdur Steinthorsdottir, Rona J Strawbridge, Yun Ju Sung, Ioanna Tachmazidou, Toshiko Tanaka, Gudmar Thorleifsson, Stella Trompet, Natalia Pervjakova, Jonathan P Tyrer, Liesbeth Vandenput, Sander W van der Laan, Nathalie van der Velde, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Efthymia Vlachopoulou, Lindsay L Waite, Sophie R Wang, Zhaoming Wang, Sarah H Wild, Christina Willenborg, James F Wilson, Andrew Wong, Jian Yang, Loïc Yengo, Laura M Yerges-Armstrong, Lei Yu, Weihua Zhang, Jing Hua Zhao, Ehm A Andersson, Stephan J L Bakker, Damiano Baldassarre, Karina Banasik, Matteo Barcella, Cristina Barlassina, Claire Bellis, Paola Benaglio, John Blangero, Matthias Blüher, Fabrice Bonnet, Lori L Bonnycastle, Heather A Boyd, Marcel Bruinenberg, Aron S Buchman, Harry Campbell, Yii-Der Ida Chen, Peter S Chines, Simone Claudi-Boehm, John Cole, Francis S Collins, Eco J C de Geus, Lisette C P G M de Groot, Maria Dimitriou, Jubao Duan, Stefan Enroth, Elodie Eury, Aliki-Eleni Farmaki, Nita G Forouhi, Nele Friedrich, Pablo V Gejman, Bruna Gigante, Nicola Glorioso, Alan S Go, Omri Gottesman, Jürgen Gräßler, Harald Grallert, Niels Grarup, Yu-Mei Gu, Linda Broer, Annelies C Ham, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew T Hattersley, Andrew C Heath, Anjali K Henders, Dena Hernandez, Hans Hillege, Oddgeir Holmen, Kees G Hovingh, Jennie Hui, Lise L Husemoen, Nina Hutri-Kähönen, Pirro G Hysi, Thomas Illig, Philip L De Jager, Shapour Jalilzadeh, Torben Jørgensen, J Wouter Jukema, Markus Juonala, Stavroula Kanoni, Maria Karaleftheri, Kay Tee Khaw, Leena Kinnunen, Steven J Kittner, Wolfgang Koenig, Ivana Kolcic, Peter Kovacs, Nikolaj T Krarup, Wolfgang Kratzer, Janine Krüger, Diana Kuh, Meena Kumari, Theodosios Kyriakou, Claudia Langenberg, Lars Lannfelt, Chiara Lanzani, Vaneet Lotay, Lenore J Launer, Karin Leander, Jaana Lindström, Allan Linneberg, Yan-Ping Liu, Stéphane Lobbens, Robert Luben, Valeriya Lyssenko, Satu Männistö, Patrik K Magnusson, Wendy L McArdle, Cristina Menni, Sigrun Merger, Lili Milani, Grant W Montgomery, Andrew P Morris, Narisu Narisu, Mari Nelis, Ken K Ong, Aarno Palotie, Louis Pérusse, Irene Pichler, Maria G Pilia, Anneli Pouta, Myriam Rheinberger, Rasmus Ribel-Madsen, Marcus Richards, Kenneth M Rice, Treva K Rice, Carlo Rivolta, Veikko Salomaa, Alan R Sanders, Mark A Sarzynski, Salome Scholtens, Robert A Scott, William R Scott, Sylvain Sebert, Sebanti Sengupta, Bengt Sennblad, Thomas Seufferlein, Angela Silveira, P Eline Slagboom, Jan H Smit, Thomas H Sparsø, Kathleen Stirrups, Ronald P Stolk, Heather M Stringham, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Emmanouil Tsafantakis, Peter J van der Most, Uwe Völker, Marie-Claude Vohl, Judith M Vonk, Melanie Waldenberger, Ryan W Walker, Roman Wennauer, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Alan F Wright, M Carola Zillikens, Suzanne C van Dijk, Natasja M van Schoor, Folkert W Asselbergs, Paul I W de Bakker, Jacques S Beckmann, John Beilby, David A Bennett, Richard N Bergman, Sven Bergmann, Carsten A Böger, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, John C Chambers, Stephen J Chanock, Daniel I Chasman, Francesco Cucca, Daniele Cusi, George Dedoussis, Jeanette Erdmann, Johan G Eriksson, Denis A Evans, Ulf de Faire, Martin Farrall, Luigi Ferrucci, Ian Ford, Lude Franke, Paul W Franks, Philippe Froguel, Ron T Gansevoort, Christian Gieger, Henrik Grönberg, Vilmundur Gudnason, Ulf Gyllensten, Per Hall, Anders Hamsten, Pim van der Harst, Caroline Hayward, Markku Heliövaara, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Frank Hu, Heikki V Huikuri, Kristian Hveem, Alan L James, Joanne M Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Sekar Kathiresan, Lambertus A L M Kiemeney, Mika Kivimaki, Paul B Knekt, Heikki A Koistinen, Jaspal S Kooner, Seppo Koskinen, Johanna Kuusisto, Winfried Maerz, Nicholas G Martin, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Guillaume Lettre, Douglas F Levinson, Lars Lind, Marja-Liisa Lokki, Pekka Mäntyselkä, Mads Melbye, Andres Metspalu, Braxton D Mitchell, Frans L Moll, Jeffrey C Murray, Arthur W Musk, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Ben A Oostra, Lyle J Palmer, James S Pankow, Gerard Pasterkamp, Nancy L Pedersen, Oluf Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P Pramstaller, Bruce M Psaty, Lu Qi, Thomas Quertermous, Olli T Raitakari, Tuomo Rankinen, Rainer Rauramaa, Paul M Ridker, John D Rioux, Fernando Rivadeneira, Jerome I Rotter, Igor Rudan, Hester M den Ruijter, Juha Saltevo, Naveed Sattar, Heribert Schunkert, Peter E H Schwarz, Alan R Shuldiner, Juha Sinisalo, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Jan A Staessen, Bandinelli Stefania, Unnur Thorsteinsdottir, Michael Stumvoll, Jean-Claude Tardif, Elena Tremoli, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, André L M Verbeek, Sita H Vermeulen, Jorma S Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Gérard Waeber, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, Eleftheria Zeggini, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Aravinda Chakravarti, Deborah J Clegg, L Adrienne Cupples, Penny Gordon-Larsen, Cashell E Jaquish, D C Rao, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Sonja I Berndt, Michael Boehnke, Panos Deloukas, Caroline S Fox, Leif C Groop, David J Hunter, Erik Ingelsson, Robert C Kaplan, Mark I McCarthy, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Joel N Hirschhorn, Cecilia M Lindgren, Iris M Heid, Kari E North, Ingrid B Borecki, Zoltán Kutalik, and Ruth J F Loos

Subjects
Genetics, QH426-470
Abstract

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR

Published
2015
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177. Season of birth is associated with birth weight, pubertal timing, adult body size and educational attainment: a UK Biobank study

Author

Felix R. Day, Nita G. Forouhi, Ken K. Ong, and John R.B. Perry

Subjects
Puberty, Seasonality, Epidemiology, Vitamin D, Sunlight, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Season of birth, a marker of in utero vitamin D exposure, has been associated with a wide range of health outcomes. Using a dataset of ∼450,000 participants from the UK Biobank study, we aimed to assess the impact of this seasonality on birth weight, age at menarche, adult height and body mass index (BMI). Birth weight, age at menarche and height, but not BMI, were highly significantly associated with season of birth. Individuals born in summer (June–July–August) had higher mean birth weight (P = 8 × 10−10), later pubertal development (P = 1.1 × 10−45) and taller adult height (P = 6.5 × 10−9) compared to those born in all other seasons. Concordantly, those born in winter (December–January–February) showed directionally opposite differences in these outcomes. A secondary comparison of the extreme differences between months revealed higher odds ratios [95% confidence intervals (CI)] for low birth weight in February vs. September (1.23 [1.15–1.32], P = 4.4 × 10−10), for early puberty in September vs. July (1.22 [1.16–1.28], P = 7.3 × 10−15) and for short stature in December vs. June (1.09 [1.03–1.17], P = 0.006). The above associations were also seen with total hours of sunshine during the second trimester, but not during the first three months after birth. Additional associations were observed with educational attainment; individuals born in autumn vs. summer were more likely to continue in education post age 16 years (P = 1.1 × 10−91) or attain a degree-level qualification (P = 4 × 10−7). However, unlike other outcomes, an abrupt difference was seen between those born in August vs. September, which flank the start of the school year. Our findings provide support for the ‘fetal programming’ hypothesis, refining and extending the impact that season of birth has on childhood growth and development. Whilst other mechanisms may contribute to these associations, these findings are consistent with a possible role of in utero vitamin D exposure.

Published
2015
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178. The impact of health behaviours on incident cardiovascular disease in Europeans and South Asians--a prospective analysis in the UK SABRE study.

Author

Anne Eriksen, Therese Tillin, Laura O'Connor, Soren Brage, Alun Hughes, Jamil Mayet, Paul McKeigue, Peter Whincup, Nish Chaturvedi, and Nita G Forouhi

Subjects
Medicine, Science
Abstract

There is consistent evidence on the impact of health behaviours on risk of cardiovascular disease (CVD) in European populations. As South Asians in the UK have an excess risk of CVD and coronary heart disease (CHD) compared to Europeans, we investigated whether a similar association between combined health behaviours and risk of CVD and CHD among this high-risk group exists, and estimated the population impact.In a prospective cohort of 1090 Europeans and 1006 South Asians (40-69 y) without prevalent CVD at baseline (1988-1990), followed up for 21 years to 2011, there were 601 incident CVD events [Europeans n = 255; South Asians n = 346] of which 520 were CHD events [n = 207 and 313 respectively]. Participants scored between 0 to 4 points for a composite score including four baseline healthy behaviours (non-smoker, moderate alcohol intake, physically active, frequent fruit/vegetable intake). Adjusted hazard ratios (95% confidence intervals) for incident CHD in Europeans who had three, two, one, and zero compared to four health behaviours were 1.33 (0.78-2.29), 1.96 (1.15-3.33), 1.36 (0.74-2.48) and 2.45 (1.18-5.10), respectively, p-trend = 0.025. In South Asians, corresponding HRs were 2.88 (1.33-6.24), 2.28 (1.06-4.91), 3.36 (1.53-7.39) and 3.48 (1.38-8.81), p-trend = 0.022. The results were similar for incident CVD; Europeans HR 2.12 (1.14-3.94), p-trend = 0.014; South Asians HR 2.73 (1.20-6.21), p-trend = 0.018. The population attributable fraction in Europeans was 43% for CHD and 28% for CVD. In South Asians it was 63% and 51% respectively.Lack of adherence to four combined health behaviours was associated with 2 to 3-fold increased risk of incident CVD in Europeans and South Asians. A substantial population impact in the South Asian group indicates important potential for disease prevention in this high-risk group by adherence to healthy behaviours.

Published
2015
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179. Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

Author

Claudia Langenberg, Stephen J Sharp, Paul W Franks, Robert A Scott, Panos Deloukas, Nita G Forouhi, Philippe Froguel, Leif C Groop, Torben Hansen, Luigi Palla, Oluf Pedersen, Matthias B Schulze, Maria-Jose Tormo, Eleanor Wheeler, Claudia Agnoli, Larraitz Arriola, Aurelio Barricarte, Heiner Boeing, Geraldine M Clarke, Françoise Clavel-Chapelon, Eric J Duell, Guy Fagherazzi, Rudolf Kaaks, Nicola D Kerrison, Timothy J Key, Kay Tee Khaw, Janine Kröger, Martin Lajous, Andrew P Morris, Carmen Navarro, Peter M Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, María-José Sánchez, Nadia Slimani, Annemieke M W Spijkerman, Rosario Tumino, Daphne L van der A, Yvonne T van der Schouw, Inês Barroso, Mark I McCarthy, Elio Riboli, and Nicholas J Wareham

Subjects
Medicine
Abstract

BackgroundUnderstanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.Methods and findingsThe InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction = 1.50×10-3) and waist circumference (p for interaction = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score.ConclusionsThe relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Published
2014
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180. The association between dietary energy density and type 2 diabetes in Europe: results from the EPIC-InterAct Study.

Author

InterAct Consortium, Saskia W van den Berg, Daphne L van der A, Annemieke M W Spijkerman, Geertruida J van Woudenbergh, Mariken J Tijhuis, Pilar Amiano, Eva Ardanaz, Joline W J Beulens, Heiner Boeing, Françoise Clavel-Chapelon, Francesca L Crowe, Blandine de Lauzon-Guillain, Guy Fagherazzi, Paul W Franks, Heinz Freisling, Carlos Gonzalez, Sara Grioni, Jytte Halkjaer, José María Huerta, Inge Huybrechts, Rudolf Kaaks, Kay Tee Khaw, Giovanna Masala, Peter M Nilsson, Kim Overvad, Salvatore Panico, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, María-José Sánchez, Matthias B Schulze, Nadia Slimani, Ellen A Struijk, Anne Tjonneland, Rosario Tumino, Stephen J Sharp, Claudia Langenberg, Nita G Forouhi, Edith J M Feskens, Elio Riboli, and Nicholas J Wareham

Subjects
Medicine, Science
Abstract

BACKGROUND:Observational studies implicate higher dietary energy density (DED) as a potential risk factor for weight gain and obesity. It has been hypothesized that DED may also be associated with risk of type 2 diabetes (T2D), but limited evidence exists. Therefore, we investigated the association between DED and risk of T2D in a large prospective study with heterogeneity of dietary intake. METHODOLOGY/PRINCIPAL FINDINGS:A case-cohort study was nested within the European Prospective Investigation into Cancer (EPIC) study of 340,234 participants contributing 3.99 million person years of follow-up, identifying 12,403 incident diabetes cases and a random subcohort of 16,835 individuals from 8 European countries. DED was calculated as energy (kcal) from foods (except beverages) divided by the weight (gram) of foods estimated from dietary questionnaires. Prentice-weighted Cox proportional hazard regression models were fitted by country. Risk estimates were pooled by random effects meta-analysis and heterogeneity was evaluated. Estimated mean (sd) DED was 1.5 (0.3) kcal/g among cases and subcohort members, varying across countries (range 1.4-1.7 kcal/g). After adjustment for age, sex, smoking, physical activity, alcohol intake, energy intake from beverages and misreporting of dietary intake, no association was observed between DED and T2D (HR 1.02 (95% CI: 0.93-1.13), which was consistent across countries (I(2) = 2.9%). CONCLUSIONS/SIGNIFICANCE:In this large European case-cohort study no association between DED of solid and semi-solid foods and risk of T2D was observed. However, despite the fact that there currently is no conclusive evidence for an association between DED and T2DM risk, choosing low energy dense foods should be promoted as they support current WHO recommendations to prevent chronic diseases.

Published
2013
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181. Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-InterAct case-cohort study.

Author

InterAct Consortium, Claudia Langenberg, Stephen J Sharp, Matthias B Schulze, Olov Rolandsson, Kim Overvad, Nita G Forouhi, Joachim Spranger, Dagmar Drogan, José María Huerta, Larraitz Arriola, Blandine de Lauzon-Guillan, Maria-Jose Tormo, Eva Ardanaz, Beverley Balkau, Joline W J Beulens, Heiner Boeing, H Bas Bueno-de-Mesquita, Françoise Clavel-Chapelon, Francesca L Crowe, Paul W Franks, Carlos A Gonzalez, Sara Grioni, Jytte Halkjaer, Goran Hallmans, Rudolf Kaaks, Nicola D Kerrison, Timothy J Key, Kay Tee Khaw, Amalia Mattiello, Peter Nilsson, Teresa Norat, Luigi Palla, Domenico Palli, Salvatore Panico, J Ramón Quirós, Dora Romaguera, Isabelle Romieu, Carlotta Sacerdote, María-José Sánchez, Nadia Slimani, Ivonne Sluijs, Annemieke M W Spijkerman, Birgit Teucher, Anne Tjonneland, Rosario Tumino, Daphne L van der A, Yvonne T van der Schouw, Edith J M Feskens, Elio Riboli, and Nicholas J Wareham

Subjects
Medicine
Abstract

BackgroundWaist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI).Methods and findingsThe prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women).ConclusionsWC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.

Published
2012
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182. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Author

Zari Dastani, Marie-France Hivert, Nicholas Timpson, John R B Perry, Xin Yuan, Robert A Scott, Peter Henneman, Iris M Heid, Jorge R Kizer, Leo-Pekka Lyytikäinen, Christian Fuchsberger, Toshiko Tanaka, Andrew P Morris, Kerrin Small, Aaron Isaacs, Marian Beekman, Stefan Coassin, Kurt Lohman, Lu Qi, Stavroula Kanoni, James S Pankow, Hae-Won Uh, Ying Wu, Aurelian Bidulescu, Laura J Rasmussen-Torvik, Celia M T Greenwood, Martin Ladouceur, Jonna Grimsby, Alisa K Manning, Ching-Ti Liu, Jaspal Kooner, Vincent E Mooser, Peter Vollenweider, Karen A Kapur, John Chambers, Nicholas J Wareham, Claudia Langenberg, Rune Frants, Ko Willems-Vandijk, Ben A Oostra, Sara M Willems, Claudia Lamina, Thomas W Winkler, Bruce M Psaty, Russell P Tracy, Jennifer Brody, Ida Chen, Jorma Viikari, Mika Kähönen, Peter P Pramstaller, David M Evans, Beate St Pourcain, Naveed Sattar, Andrew R Wood, Stefania Bandinelli, Olga D Carlson, Josephine M Egan, Stefan Böhringer, Diana van Heemst, Lyudmyla Kedenko, Kati Kristiansson, Marja-Liisa Nuotio, Britt-Marie Loo, Tamara Harris, Melissa Garcia, Alka Kanaya, Margot Haun, Norman Klopp, H-Erich Wichmann, Panos Deloukas, Efi Katsareli, David J Couper, Bruce B Duncan, Margreet Kloppenburg, Linda S Adair, Judith B Borja, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, James G Wilson, Solomon Musani, Xiuqing Guo, Toby Johnson, Robert Semple, Tanya M Teslovich, Matthew A Allison, Susan Redline, Sarah G Buxbaum, Karen L Mohlke, Ingrid Meulenbelt, Christie M Ballantyne, George V Dedoussis, Frank B Hu, Yongmei Liu, Bernhard Paulweber, Timothy D Spector, P Eline Slagboom, Luigi Ferrucci, Antti Jula, Markus Perola, Olli Raitakari, Jose C Florez, Veikko Salomaa, Johan G Eriksson, Timothy M Frayling, Andrew A Hicks, Terho Lehtimäki, George Davey Smith, David S Siscovick, Florian Kronenberg, Cornelia van Duijn, Ruth J F Loos, Dawn M Waterworth, James B Meigs, Josee Dupuis, J Brent Richards, Benjamin F Voight, Laura J Scott, Valgerdur Steinthorsdottir, Christian Dina, Ryan P Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S Aulchenko, Gudmar Thorleifsson, Laura J McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J Willer, Soumya Raychaudhuri, Steve A McCarroll, Oliver M Hofmann, Ayellet V Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J Bennett, Roza Blagieva, Eric Boerwinkle, Lori L Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noël P Burtt, Guillaume Charpentier, Peter S Chines, Marilyn Cornelis, Gabe Crawford, Alex S F Doney, Katherine S Elliott, Amanda L Elliott, Michael R Erdos, Caroline S Fox, Christopher S Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U Jackson, Paul R V Johnson, Torben Jørgensen, Wen H L Kao, Augustine Kong, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A Morken, Narisu Narisu, Peter Nilsson, Katharine R Owen, Felicity Payne, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N William Rayner, Neil R Robertson, Ghislain Rocheleau, Michael Roden, Michael J Sampson, Richa Saxena, Beverley M Shields, Peter Shrader, Gunnar Sigurdsson, Thomas Sparsø, Klaus Strassburger, Heather M Stringham, Qi Sun, Amy J Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob M van Dam, Timon W van Haeften, Thijs van Herpt, Jana V van Vliet-Ostaptchouk, G Bragi Walters, Michael N Weedon, Cisca Wijmenga, Jacqueline Witteman, Richard N Bergman, Stephane Cauchi, Francis S Collins, Anna L Gloyn, Ulf Gyllensten, Torben Hansen, Winston A Hide, Graham A Hitman, Albert Hofman, David J Hunter, Kristian Hveem, Markku Laakso, Andrew D Morris, Colin N A Palmer, Igor Rudan, Eric Sijbrands, Lincoln D Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Richard M Watanabe, Goncalo R Abecasis, Bernhard O Boehm, Harry Campbell, Mark J Daly, Andrew T Hattersley, Oluf Pedersen, Inês Barroso, Leif Groop, Rob Sladek, Unnur Thorsteinsdottir, James F Wilson, Thomas Illig, Philippe Froguel, Cornelia M van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I McCarthy, Nicole Soranzo, Eleanor Wheeler, Nicole L Glazer, Nabila Bouatia-Naji, Reedik Mägi, Joshua Randall, Paul Elliott, Denis Rybin, Abbas Dehghan, Jouke Jan Hottenga, Kijoung Song, Anuj Goel, Taina Lajunen, Alex Doney, Christine Cavalcanti-Proença, Meena Kumari, Nicholas J Timpson, Carina Zabena, Erik Ingelsson, Ping An, Jeffrey O'Connell, Jian'an Luan, Amanda Elliott, Steven A McCarroll, Rosa Maria Roccasecca, François Pattou, Praveen Sethupathy, Yavuz Ariyurek, Philip Barter, John P Beilby, Yoav Ben-Shlomo, Sven Bergmann, Murielle Bochud, Amélie Bonnefond, Knut Borch-Johnsen, Yvonne Böttcher, Eric Brunner, Suzannah J Bumpstead, Yii-Der Ida Chen, Peter Chines, Robert Clarke, Lachlan J M Coin, Matthew N Cooper, Laura Crisponi, Ian N M Day, Eco J C de Geus, Jerome Delplanque, Annette C Fedson, Antje Fischer-Rosinsky, Nita G Forouhi, Maria Grazia Franzosi, Pilar Galan, Mark O Goodarzi, Jürgen Graessler, Scott Grundy, Rhian Gwilliam, Göran Hallmans, Naomi Hammond, Xijing Han, Anna-Liisa Hartikainen, Caroline Hayward, Simon C Heath, Serge Hercberg, David R Hillman, Aroon D Hingorani, Jennie Hui, Joe Hung, Marika Kaakinen, Jaakko Kaprio, Y Antero Kesaniemi, Mika Kivimaki, Beatrice Knight, Seppo Koskinen, Peter Kovacs, Kirsten Ohm Kyvik, G Mark Lathrop, Debbie A Lawlor, Olivier Le Bacquer, Cécile Lecoeur, Yun Li, Robert Mahley, Massimo Mangino, María Teresa Martínez-Larrad, Jarred B McAteer, Ruth McPherson, Christa Meisinger, David Melzer, David Meyre, Braxton D Mitchell, Sutapa Mukherjee, Silvia Naitza, Matthew J Neville, Marco Orrù, Ruth Pakyz, Giuseppe Paolisso, Cristian Pattaro, Daniel Pearson, John F Peden, Nancy L Pedersen, Andreas F H Pfeiffer, Irene Pichler, Ozren Polasek, Danielle Posthuma, Simon C Potter, Anneli Pouta, Michael A Province, Nigel W Rayner, Kenneth Rice, Samuli Ripatti, Fernando Rivadeneira, Olov Rolandsson, Annelli Sandbaek, Manjinder Sandhu, Serena Sanna, Avan Aihie Sayer, Paul Scheet, Udo Seedorf, Stephen J Sharp, Beverley Shields, Gunnar Sigurðsson, Eric J G Sijbrands, Angela Silveira, Laila Simpson, Andrew Singleton, Nicholas L Smith, Ulla Sovio, Amy Swift, Holly Syddall, Ann-Christine Syvänen, Anke Tönjes, André G Uitterlinden, Ko Willems van Dijk, Dhiraj Varma, Sophie Visvikis-Siest, Veronique Vitart, Nicole Vogelzangs, Gérard Waeber, Peter J Wagner, Andrew Walley, Kim L Ward, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, Jaqueline C M Witteman, John W G Yarnell, Diana Zelenika, Björn Zethelius, Guangju Zhai, Jing Hua Zhao, M Carola Zillikens, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Ingrid B Borecki, Pierre Meneton, Patrik K E Magnusson, David M Nathan, Gordon H Williams, Kaisa Silander, Stefan R Bornstein, Peter Schwarz, Joachim Spranger, Fredrik Karpe, Alan R Shuldiner, Cyrus Cooper, Manuel Serrano-Ríos, Lars Lind, Lyle J Palmer, Paul W Franks, Shah Ebrahim, Michael Marmot, W H Linda Kao, Peter Paul Pramstaller, Alan F Wright, Michael Stumvoll, Anders Hamsten, Procardis Consortium, Thomas A Buchanan, Timo T Valle, Jerome I Rotter, Brenda W J H Penninx, Dorret I Boomsma, Antonio Cao, Angelo Scuteri, David Schlessinger, Manuela Uda, Aimo Ruokonen, Marjo-Riitta Jarvelin, Leena Peltonen, Vincent Mooser, Robert Sladek, MAGIC investigators, GLGC Consortium, Kiran Musunuru, Albert V Smith, Andrew C Edmondson, Ioannis M Stylianou, Masahiro Koseki, James P Pirruccello, Daniel I Chasman, Christopher T Johansen, Sigrid W Fouchier, Gina M Peloso, Maja Barbalic, Sally L Ricketts, Joshua C Bis, Mary F Feitosa, Marju Orho-Melander, Olle Melander, Xiaohui Li, Mingyao Li, Yoon Shin Cho, Min Jin Go, Young Jin Kim, Jong-Young Lee, Taesung Park, Kyunga Kim, Xueling Sim, Rick Twee-Hee Ong, Damien C Croteau-Chonka, Leslie A Lange, Joshua D Smith, Andreas Ziegler, Weihua Zhang, Robert Y L Zee, John B Whitfield, John R Thompson, Ida Surakka, Tim D Spector, Johannes H Smit, Juha Sinisalo, James Scott, Juha Saharinen, Chiara Sabatti, Lynda M Rose, Robert Roberts, Mark Rieder, Alex N Parker, Guillaume Pare, Christopher J O'Donnell, Markku S Nieminen, Deborah A Nickerson, Grant W Montgomery, Wendy McArdle, David Masson, Nicholas G Martin, Fabio Marroni, Gavin Lucas, Robert Luben, Marja-Liisa Lokki, Guillaume Lettre, Lenore J Launer, Edward G Lakatta, Reijo Laaksonen, Kirsten O Kyvik, Inke R König, Kay-Tee Khaw, Lee M Kaplan, Åsa Johansson, A Cecile J W Janssens, Wilmar Igl, G Kees Hovingh, Christian Hengstenberg, Aki S Havulinna, Nicholas D Hastie, Tamara B Harris, Talin Haritunians, Alistair S Hall, Leif C Groop, Elena Gonzalez, Nelson B Freimer, Jeanette Erdmann, Kenechi G Ejebe, Angela Döring, Anna F Dominiczak, Serkalem Demissie, Panagiotis Deloukas, Ulf de Faire, Gabriel Crawford, Yii-der I Chen, Mark J Caulfield, S Matthijs Boekholdt, Themistocles L Assimes, Thomas Quertermous, Mark Seielstad, Tien Y Wong, E-Shyong Tai, Alan B Feranil, Christopher W Kuzawa, Herman A Taylor, Stacey B Gabriel, Hilma Holm, Vilmundur Gudnason, Ronald M Krauss, Jose M Ordovas, Patricia B Munroe, Jaspal S Kooner, Alan R Tall, Robert A Hegele, John J P Kastelein, Eric E Schadt, David P Strachan, Muredach P Reilly, Nilesh J Samani, Heribert Schunkert, L Adrienne Cupples, Manjinder S Sandhu, Paul M Ridker, Daniel J Rader, and Sekar Kathiresan

Subjects
Genetics, QH426-470
Abstract

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

Published
2012
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183. Tea consumption and incidence of type 2 diabetes in Europe: the EPIC-InterAct case-cohort study.

Author

InterAct Consortium, Geertruida J van Woudenbergh, Anneleen Kuijsten, Dagmar Drogan, Daphne L van der A, Dora Romaguera, Eva Ardanaz, Pilar Amiano, Aurelio Barricarte, Joline W J Beulens, Heiner Boeing, H Bas Bueno-de-Mesquita, Christina C Dahm, M-Doleres Chirlaque, Francoise Clavel, Francesca L Crowe, Piia-Piret Eomois, Guy Fagherazzi, Paul W Franks, Jytte Halkjaer, Kay T Khaw, Giovanna Masala, Amalia Mattiello, Peter Nilsson, Kim Overvad, J Ramón Quirós, Olov Rolandsson, Isabelle Romieu, Carlotta Sacerdote, María-José Sánchez, Matthias B Schulze, Nadia Slimani, Ivonne Sluijs, Annemieke M W Spijkerman, Giovanna Tagliabue, Anne Tjønneland, Rosario Tumino, Nita G Forouhi, Stephen Sharp, Claudia Langenberg, Edith J M Feskens, Elio Riboli, and Nicholas J Wareham

Subjects
Medicine, Science
Abstract

In previous meta-analyses, tea consumption has been associated with lower incidence of type 2 diabetes. It is unclear, however, if tea is associated inversely over the entire range of intake. Therefore, we investigated the association between tea consumption and incidence of type 2 diabetes in a European population.The EPIC-InterAct case-cohort study was conducted in 26 centers in 8 European countries and consists of a total of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,835 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Country-specific Hazard Ratios (HR) for incidence of type 2 diabetes were obtained after adjustment for lifestyle and dietary factors using a Cox regression adapted for a case-cohort design. Subsequently, country-specific HR were combined using a random effects meta-analysis. Tea consumption was studied as categorical variable (0, >0-

Published
2012
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184. Ethnic differences in disability prevalence and their determinants studied over a 20-year period: a cohort study.

Author

Emily D Williams, Therese Tillin, Peter Whincup, Nita G Forouhi, and Nishi Chaturvedi

Subjects
Medicine, Science
Abstract

BACKGROUND:To compare disability prevalence rates in the major ethnic groups in the UK and understand the risk factors contributing to differences identified. It was hypothesised that Indian Asian and African Caribbean people would experience higher rates of disability compared with Europeans. METHODS:Data was collected from 888 European, 636 Indian Asian and 265 African Caribbean men and women, aged 58-88 years at 20-year follow-up of community-based cohort study, based in West London. Disability was measured using a performance-based locomotor function test and self-reported questionnaires on functional limitation, and instrumental (IADL) and basic activities of daily living (ADL). RESULTS:The mean (SD) age of participants at follow-up was 69.6 (6.2) years. Compared with Europeans, Indian Asian people were significantly more likely to experience all of the disability outcomes than Europeans; this persisted after adjustment for socioeconomic, behavioural, adiposity and chronic disease risk factors measured at baseline (locomotor dysfunction: adjusted odds ratio (OR) 2.20, 95% CI 1.56-3.11; functional limitation: OR 2.77, 2.01-3.81; IADL impairment: OR 3.12, 2.20-4.41; ADL impairment: OR 1.58, 1.11-2.24). In contrast, a modest excess risk of disability was observed in African Caribbeans, which was abolished after adjustment (e.g. locomotor dysfunction: OR 1.37, 0.90-1.91); indeed a reduced risk of ADL impairment appeared after multivariable adjustment (OR from 0.99, 0.68-1.45 to 0.59, 0.38-0.93), compared with Europeans. CONCLUSIONS:Substantially elevated risk of disability was observed among Indian Asian participants, unexplained by known factors. A greater understanding of determinants of disability and normative functional beliefs of healthy aging is required in this population to inform intervention efforts to prevent disability.

Published
2012
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185. A genome-wide association search for type 2 diabetes genes in African Americans.

Author

Nicholette D Palmer, Caitrin W McDonough, Pamela J Hicks, Bong H Roh, Maria R Wing, S Sandy An, Jessica M Hester, Jessica N Cooke, Meredith A Bostrom, Megan E Rudock, Matthew E Talbert, Joshua P Lewis, DIAGRAM Consortium, MAGIC Investigators, Assiamira Ferrara, Lingyi Lu, Julie T Ziegler, Michele M Sale, Jasmin Divers, Daniel Shriner, Adebowale Adeyemo, Charles N Rotimi, Maggie C Y Ng, Carl D Langefeld, Barry I Freedman, Donald W Bowden, Benjamin F Voight, Laura J Scott, Valgerdur Steinthorsdottir, Andrew P Morris, Christian Dina, Ryan P Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S Aulchenko, Gudmar Thorleifsson, Laura J McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J Willer, Soumya Raychaudhuri, Steve A McCarroll, Claudia Langenberg, Oliver M Hofmann, Josée Dupuis, Lu Qi, Ayellet V Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J Bennett, Roza Blagieva, Eric Boerwinkle, Lori L Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noël P Burtt, Guillaume Charpentier, Peter S Chines, Marilyn Cornelis, David J Couper, Gabe Crawford, Alex S F Doney, Katherine S Elliott, Amanda L Elliott, Michael R Erdos, Caroline S Fox, Christopher S Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U Jackson, Paul R V Johnson, Torben Jørgensen, Wen H L Kao, Norman Klopp, Augustine Kong, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A Morken, Narisu Narisu, Peter Nilsson, Katharine R Owen, Felicity Payne, John R B Perry, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N William Rayner, Neil R Robertson, Ghislain Rocheleau, Michael Roden, Michael J Sampson, Richa Saxena, Beverley M Shields, Peter Shrader, Gunnar Sigurdsson, Thomas Sparsø, Klaus Strassburger, Heather M Stringham, Qi Sun, Amy J Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob M van Dam, Timon W van Haeften, Thijs van Herpt, Jana V van Vliet-Ostaptchouk, G Bragi Walters, Michael N Weedon, Cisca Wijmenga, Jacqueline Witteman, Richard N Bergman, Stephane Cauchi, Francis S Collins, Anna L Gloyn, Ulf Gyllensten, Torben Hansen, Winston A Hide, Graham A Hitman, Albert Hofman, David J Hunter, Kristian Hveem, Markku Laakso, Karen L Mohlke, Andrew D Morris, Colin N A Palmer, Peter P Pramstaller, Igor Rudan, Eric Sijbrands, Lincoln D Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Nicholas J Wareham, Richard M Watanabe, Goncalo R Abecasis, Bernhard O Boehm, Harry Campbell, Mark J Daly, Andrew T Hattersley, Frank B Hu, James B Meigs, James S Pankow, Oluf Pedersen, H-Erich Wichmann, Inês Barroso, Jose C Florez, Timothy M Frayling, Leif Groop, Rob Sladek, Unnur Thorsteinsdottir, James F Wilson, Thomas Illig, Philippe Froguel, Cornelia M van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I McCarthy, Nicole Soranzo, Eleanor Wheeler, Nicole L Glazer, Nabila Bouatia-Naji, Reedik Mägi, Joshua Randall, Toby Johnson, Paul Elliott, Denis Rybin, Peter Henneman, Abbas Dehghan, Jouke Jan Hottenga, Kijoung Song, Anuj Goel, Josephine M Egan, Taina Lajunen, Alex Doney, Stavroula Kanoni, Christine Cavalcanti-Proença, Meena Kumari, Nicholas J Timpson, Carina Zabena, Erik Ingelsson, Ping An, Jeffrey O'Connell, Jian'an Luan, Amanda Elliott, Steven A McCarroll, Rosa Maria Roccasecca, François Pattou, Praveen Sethupathy, Yavuz Ariyurek, Philip Barter, John P Beilby, Yoav Ben-Shlomo, Sven Bergmann, Murielle Bochud, Amélie Bonnefond, Knut Borch-Johnsen, Yvonne Böttcher, Eric Brunner, Suzannah J Bumpstead, Yii-Der Ida Chen, Peter Chines, Robert Clarke, Lachlan J M Coin, Matthew N Cooper, Laura Crisponi, Ian N M Day, Eco J C de Geus, Jerome Delplanque, Annette C Fedson, Antje Fischer-Rosinsky, Nita G Forouhi, Rune Frants, Maria Grazia Franzosi, Pilar Galan, Mark O Goodarzi, Jürgen Graessler, Scott Grundy, Rhian Gwilliam, Göran Hallmans, Naomi Hammond, Xijing Han, Anna-Liisa Hartikainen, Caroline Hayward, Simon C Heath, Serge Hercberg, Andrew A Hicks, David R Hillman, Aroon D Hingorani, Jennie Hui, Joe Hung, Antti Jula, Marika Kaakinen, Jaakko Kaprio, Y Antero Kesaniemi, Mika Kivimaki, Beatrice Knight, Seppo Koskinen, Peter Kovacs, Kirsten Ohm Kyvik, G Mark Lathrop, Debbie A Lawlor, Olivier Le Bacquer, Cécile Lecoeur, Yun Li, Robert Mahley, Massimo Mangino, Alisa K Manning, María Teresa Martínez-Larrad, Jarred B McAteer, Ruth McPherson, Christa Meisinger, David Melzer, David Meyre, Braxton D Mitchell, Sutapa Mukherjee, Silvia Naitza, Matthew J Neville, Ben A Oostra, Marco Orrù, Ruth Pakyz, Giuseppe Paolisso, Cristian Pattaro, Daniel Pearson, John F Peden, Nancy L Pedersen, Markus Perola, Andreas F H Pfeiffer, Irene Pichler, Ozren Polasek, Danielle Posthuma, Simon C Potter, Anneli Pouta, Michael A Province, Bruce M Psaty, Nigel W Rayner, Kenneth Rice, Samuli Ripatti, Fernando Rivadeneira, Olov Rolandsson, Annelli Sandbaek, Manjinder Sandhu, Serena Sanna, Avan Aihie Sayer, Paul Scheet, Udo Seedorf, Stephen J Sharp, Beverley Shields, Eric J G Sijbrands, Angela Silveira, Laila Simpson, Andrew Singleton, Nicholas L Smith, Ulla Sovio, Amy Swift, Holly Syddall, Ann-Christine Syvänen, Toshiko Tanaka, Anke Tönjes, André G Uitterlinden, Ko Willems van Dijk, Dhiraj Varma, Sophie Visvikis-Siest, Veronique Vitart, Nicole Vogelzangs, Gérard Waeber, Peter J Wagner, Andrew Walley, Kim L Ward, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, Jaqueline C M Witteman, John W G Yarnell, Diana Zelenika, Björn Zethelius, Guangju Zhai, Jing Hua Zhao, M Carola Zillikens, Ingrid B Borecki, Ruth J F Loos, Pierre Meneton, Patrik K E Magnusson, David M Nathan, Gordon H Williams, Kaisa Silander, Veikko Salomaa, George Davey Smith, Stefan R Bornstein, Peter Schwarz, Joachim Spranger, Fredrik Karpe, Alan R Shuldiner, Cyrus Cooper, George V Dedoussis, Manuel Serrano-Ríos, Lars Lind, Lyle J Palmer, Paul W Franks, Shah Ebrahim, Michael Marmot, W H Linda Kao, Peter Paul Pramstaller, Alan F Wright, Michael Stumvoll, Anders Hamsten, Thomas A Buchanan, Timo T Valle, Jerome I Rotter, David S Siscovick, Brenda W J H Penninx, Dorret I Boomsma, Panos Deloukas, Timothy D Spector, Luigi Ferrucci, Antonio Cao, Angelo Scuteri, David Schlessinger, Manuela Uda, Aimo Ruokonen, Marjo-Riitta Jarvelin, Dawn M Waterworth, Peter Vollenweider, Leena Peltonen, Vincent Mooser, and Robert Sladek

Subjects
Medicine, Science
Abstract

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P

Published
2012
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186. Food composition of the diet in relation to changes in waist circumference adjusted for body mass index.

Author

Dora Romaguera, Lars Ängquist, Huaidong Du, Marianne Uhre Jakobsen, Nita G Forouhi, Jytte Halkjær, Edith J M Feskens, Daphne L van der A, Giovanna Masala, Annika Steffen, Domenico Palli, Nicholas J Wareham, Kim Overvad, Anne Tjønneland, Heiner Boeing, Elio Riboli, and Thorkild I Sørensen

Subjects
Medicine, Science
Abstract

Dietary factors such as low energy density and low glycemic index were associated with a lower gain in abdominal adiposity. A better understanding of which food groups/items contribute to these associations is necessary.To ascertain the association of food groups/items consumption on prospective annual changes in "waist circumference for a given BMI" (WC(BMI)), a proxy for abdominal adiposity.We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WC(BMI) was defined as the residuals of waist circumference regressed on BMI, and annual change in WC(BMI) (ΔWC(BMI), cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between food groups/items and ΔWC(BMI) was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates.Higher fruit and dairy products consumption was associated with a lower gain in WC(BMI) whereas the consumption of white bread, processed meat, margarine, and soft drinks was positively associated with ΔWC(BMI). When these six food groups/items were analyzed in combination using a summary score, those in the highest quartile of the score--indicating a more favourable dietary pattern--showed a ΔWC(BMI) of -0.11 (95% CI -0.09 to -0.14) cm/y compared to those in the lowest quartile.A dietary pattern high in fruit and dairy and low in white bread, processed meat, margarine, and soft drinks may help to prevent abdominal fat accumulation.

Published
2011
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187. Fat oxidation, fitness and skeletal muscle expression of oxidative/lipid metabolism genes in South Asians: implications for insulin resistance?

Author

Lesley M L Hall, Colin N Moran, Gillian R Milne, John Wilson, Niall G MacFarlane, Nita G Forouhi, Narayanan Hariharan, Ian P Salt, Naveed Sattar, and Jason M R Gill

Subjects
Medicine, Science
Abstract

South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures.Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4±5.7 ml x kg(-1) x min(-1), p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77±2.02 vs 6.55±2.60 mg x kg(-1) x min(-1) at 55% VO2max, p = 0.013), and absolute (3.46±2.20 vs 6.00±1.93 mg x kg(-1) x min(-1) at 25 ml O(2) x kg(-1) x min(-1), p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10-13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity.These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.

Published
2010
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188. Differential white blood cell count and type 2 diabetes: systematic review and meta-analysis of cross-sectional and prospective studies.

Author

Effrossyni Gkrania-Klotsas, Zheng Ye, Andrew J Cooper, Stephen J Sharp, Robert Luben, Mary L Biggs, Liang-Kung Chen, Kuppan Gokulakrishnan, Markolf Hanefeld, Erik Ingelsson, Wen-An Lai, Shih-Yi Lin, Lars Lind, Vitool Lohsoonthorn, Viswanathan Mohan, Antonio Muscari, Goran Nilsson, John Ohrvik, Jiang Chao Qiang, Nancy Swords Jenny, Koji Tamakoshi, Theodora Temelkova-Kurktschiev, Ya-Yu Wang, Chittaranjan Sakerlal Yajnik, Marco Zoli, Kay-Tee Khaw, Nita G Forouhi, Nicholas J Wareham, and Claudia Langenberg

Subjects
Medicine, Science
Abstract

Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10(-18)). Substantial heterogeneity was present (I(2) = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10(-4)), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10(-13)), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10(-5)). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.

Published
2010
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189. Dietary determinants of changes in waist circumference adjusted for body mass index - a proxy measure of visceral adiposity.

Author

Dora Romaguera, Lars Angquist, Huaidong Du, Marianne Uhre Jakobsen, Nita G Forouhi, Jytte Halkjaer, Edith J M Feskens, Daphne L van der A, Giovanna Masala, Annika Steffen, Domenico Palli, Nicholas J Wareham, Kim Overvad, Anne Tjønneland, Heiner Boeing, Elio Riboli, and Thorkild I A Sørensen

Subjects
Medicine, Science
Abstract

Given the recognized health effects of visceral fat, the understanding of how diet can modulate changes in the phenotype "waist circumference for a given body mass index (WC(BMI))", a proxy measure of visceral adiposity, is deemed necessary. Hence, the objective of the present study was to assess the association between dietary factors and prospective changes in visceral adiposity as measured by changes in the phenotype WC(BMI).We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WC(BMI) was defined as the residuals of waist circumference regressed on body mass index, and annual change in WC(BMI) (DeltaWC(BMI), cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between energy, energy density (ED), macronutrients, alcohol, glycemic index (GI), glycemic load (GL), fibre and DeltaWC(BMI) was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates. Men and women with higher ED and GI diets showed significant increases in their WC(BMI), compared to those with lower ED and GI [1 kcal/g greater ED predicted a DeltaWC(BMI) of 0.09 cm (95% CI 0.05 to 0.13) in men and 0.15 cm (95% CI 0.09 to 0.21) in women; 10 units greater GI predicted a DeltaWC(BMI) of 0.07 cm (95% CI 0.03 to 0.12) in men and 0.06 cm (95% CI 0.03 to 0.10) in women]. Among women, lower fibre intake, higher GL, and higher alcohol consumption also predicted a higher DeltaWC(BMI).Results of this study suggest that a diet with low GI and ED may prevent visceral adiposity, defined as the prospective changes in WC(BMI). Additional effects may be obtained among women of low alcohol, low GL, and high fibre intake.

Published
2010
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190. Markers of dysglycaemia and risk of coronary heart disease in people without diabetes: Reykjavik prospective study and systematic review.

Author

Nadeem Sarwar, Thor Aspelund, Gudny Eiriksdottir, Reeta Gobin, Sreenivasa Rao Kondapally Seshasai, Nita G Forouhi, Gunnar Sigurdsson, John Danesh, and Vilmundur Gudnason

Subjects
Medicine
Abstract

BackgroundAssociations between circulating markers of dysglycaemia and coronary heart disease (CHD) risk in people without diabetes have not been reliably characterised. We report new data from a prospective study and a systematic review to help quantify these associations.Methods and findingsFasting and post-load glucose levels were measured in 18,569 participants in the population-based Reykjavik study, yielding 4,664 incident CHD outcomes during 23.5 y of mean follow-up. In people with no known history of diabetes at the baseline survey, the hazard ratio (HR) for CHD, adjusted for several conventional risk factors, was 2.37 (95% CI 1.79-3.14) in individuals with fasting glucose > or = 7.0 mmol/l compared to those < 7 mmol/l. At fasting glucose values below 7 mmol/l, adjusted HRs were 0.95 (0.89-1.01) per 1 mmol/l higher fasting glucose and 1.03 (1.01-1.05) per 1 mmol/l higher post-load glucose. HRs for CHD risk were generally modest and nonsignificant across tenths of glucose values below 7 mmol/l. We did a meta-analysis of 26 additional relevant prospective studies identified in a systematic review of Western cohort studies that recorded fasting glucose, post-load glucose, or glycated haemoglobin (HbA(1c)) levels. In this combined analysis, in which participants with a self-reported history of diabetes and/or fasting blood glucose > or = 7 mmol/l at baseline were excluded, relative risks for CHD, adjusted for several conventional risk factors, were: 1.06 (1.00-1.12) per 1 mmol/l higher fasting glucose (23 cohorts, 10,808 cases, 255,171 participants); 1.05 (1.03-1.07) per 1 mmol/l higher post-load glucose (15 cohorts, 12,652 cases, 102,382 participants); and 1.20 (1.10-1.31) per 1% higher HbA(1c) (9 cohorts, 1639 cases, 49,099 participants).ConclusionsIn the Reykjavik Study and a meta-analysis of other Western prospective studies, fasting and post-load glucose levels were modestly associated with CHD risk in people without diabetes. The meta-analysis suggested a somewhat stronger association between HbA(1c) levels and CHD risk.

Published
2010
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191. Correction: Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution.

Author

Cecilia M. Lindgren, Iris M. Heid, Joshua C. Randall, Claudia Lamina, Valgerdur Steinthorsdottir, Lu Qi, Elizabeth K. Speliotes, Gudmar Thorleifsson, Cristen J. Willer, Blanca M. Herrera, Anne U. Jackson, Noha Lim, Paul Scheet, Nicole Soranzo, Najaf Amin, Yurii S. Aulchenko, John C. Chambers, Alexander Drong, Jian'an Luan, Helen N. Lyon, Fernando Rivadeneira, Serena Sanna, Nicholas J. Timpson, M. Carola Zillikens, Jing Hua Zhao, Peter Almgren, Stefania Bandinelli, Amanda J. Bennett, Richard N. Bergman, Lori L. Bonnycastle, Suzannah J. Bumpstead, Stephen J. Chanock, Lynn Cherkas, Peter Chines, Lachlan Coin, Cyrus Cooper, Gabriel Crawford, Angela Doering, Anna Dominiczak, Alex S. F. Doney, Shah Ebrahim, Paul Elliott, Michael R. Erdos, Karol Estrada, Luigi Ferrucci, Guido Fischer, Nita G. Forouhi, Christian Gieger, Harald Grallert, Christopher J. Groves, Scott Grundy, Candace Guiducci, David Hadley, Anders Hamsten, Aki S. Havulinna, Albert Hofman, Rolf Holle, John W. Holloway, Thomas Illig, Bo Isomaa, Leonie C. Jacobs, Karen Jameson, Pekka Jousilahti, Fredrik Karpe, Johanna Kuusisto, Jaana Laitinen, G. Mark Lathrop, Debbie A. Lawlor, Massimo Mangino, Wendy L. McArdle, Thomas Meitinger, Mario A. Morken, Andrew P. Morris, Patricia Munroe, Narisu Narisu, Anna Nordström, Peter Nordström, Ben A. Oostra, Colin N. A. Palmer, Felicity Payne, John F. Peden, Inga Prokopenko, Frida Renström, Aimo Ruokonen, Veikko Salomaa, Manjinder S. Sandhu, Laura J. Scott, Angelo Scuteri, Kaisa Silander, Kijoung Song, Xin Yuan, Heather M. Stringham, Amy J. Swift, Tiinamaija Tuomi, Manuela Uda, Peter Vollenweider, Gerard Waeber, Chris Wallace, G. Bragi Walters, Michael N. Weedon, Jacqueline C. M. Witteman, Cuilin Zhang, Weihua Zhang, Mark J. Caulfield, Francis S. Collins, George Davey Smith, Ian N. M. Day, Paul W. Franks, Andrew T. Hattersley, Frank B. Hu, Marjo-Riitta Jarvelin, Augustine Kong, Jaspal S. Kooner, Markku Laakso, Edward Lakatta, Vincent Mooser, Andrew D. Morris, Leena Peltonen, Nilesh J. Samani, Timothy D. Spector, David P. Strachan, Toshiko Tanaka, Jaakko Tuomilehto, André G. Uitterlinden, Cornelia M. van Duijn, Nicholas J. Wareham, Hugh Watkins for the PROCARDIS consortia, Dawn M. Waterworth, Michael Boehnke, Panos Deloukas, Leif Groop, David J. Hunter, Unnur Thorsteinsdottir, David Schlessinger, H.-Erich Wichmann, Timothy M. Frayling, Gonçalo R. Abecasis, Joel N. Hirschhorn, Ruth J. F. Loos, Kari Stefansson, Karen L. Mohlke, Inês Barroso, and Mark I. McCarthy for the GIANT consortium

Subjects
Genetics, QH426-470
Published
2009
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192. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

Author

Cecilia M Lindgren, Iris M Heid, Joshua C Randall, Claudia Lamina, Valgerdur Steinthorsdottir, Lu Qi, Elizabeth K Speliotes, Gudmar Thorleifsson, Cristen J Willer, Blanca M Herrera, Anne U Jackson, Noha Lim, Paul Scheet, Nicole Soranzo, Najaf Amin, Yurii S Aulchenko, John C Chambers, Alexander Drong, Jian'an Luan, Helen N Lyon, Fernando Rivadeneira, Serena Sanna, Nicholas J Timpson, M Carola Zillikens, Jing Hua Zhao, Peter Almgren, Stefania Bandinelli, Amanda J Bennett, Richard N Bergman, Lori L Bonnycastle, Suzannah J Bumpstead, Stephen J Chanock, Lynn Cherkas, Peter Chines, Lachlan Coin, Cyrus Cooper, Gabriel Crawford, Angela Doering, Anna Dominiczak, Alex S F Doney, Shah Ebrahim, Paul Elliott, Michael R Erdos, Karol Estrada, Luigi Ferrucci, Guido Fischer, Nita G Forouhi, Christian Gieger, Harald Grallert, Christopher J Groves, Scott Grundy, Candace Guiducci, David Hadley, Anders Hamsten, Aki S Havulinna, Albert Hofman, Rolf Holle, John W Holloway, Thomas Illig, Bo Isomaa, Leonie C Jacobs, Karen Jameson, Pekka Jousilahti, Fredrik Karpe, Johanna Kuusisto, Jaana Laitinen, G Mark Lathrop, Debbie A Lawlor, Massimo Mangino, Wendy L McArdle, Thomas Meitinger, Mario A Morken, Andrew P Morris, Patricia Munroe, Narisu Narisu, Anna Nordström, Peter Nordström, Ben A Oostra, Colin N A Palmer, Felicity Payne, John F Peden, Inga Prokopenko, Frida Renström, Aimo Ruokonen, Veikko Salomaa, Manjinder S Sandhu, Laura J Scott, Angelo Scuteri, Kaisa Silander, Kijoung Song, Xin Yuan, Heather M Stringham, Amy J Swift, Tiinamaija Tuomi, Manuela Uda, Peter Vollenweider, Gerard Waeber, Chris Wallace, G Bragi Walters, Michael N Weedon, Wellcome Trust Case Control Consortium, Jacqueline C M Witteman, Cuilin Zhang, Weihua Zhang, Mark J Caulfield, Francis S Collins, George Davey Smith, Ian N M Day, Paul W Franks, Andrew T Hattersley, Frank B Hu, Marjo-Riitta Jarvelin, Augustine Kong, Jaspal S Kooner, Markku Laakso, Edward Lakatta, Vincent Mooser, Andrew D Morris, Leena Peltonen, Nilesh J Samani, Timothy D Spector, David P Strachan, Toshiko Tanaka, Jaakko Tuomilehto, André G Uitterlinden, Cornelia M van Duijn, Nicholas J Wareham, Hugh Watkins, Procardis Consortia, Dawn M Waterworth, Michael Boehnke, Panos Deloukas, Leif Groop, David J Hunter, Unnur Thorsteinsdottir, David Schlessinger, H-Erich Wichmann, Timothy M Frayling, Gonçalo R Abecasis, Joel N Hirschhorn, Ruth J F Loos, Kari Stefansson, Karen L Mohlke, Inês Barroso, Mark I McCarthy, and Giant Consortium

Subjects
Genetics, QH426-470
Abstract

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

Published
2009
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193. Dietary energy density in relation to subsequent changes of weight and waist circumference in European men and women.

Author

Huaidong Du, Daphne L van der A, Vanessa Ginder, Susan A Jebb, Nita G Forouhi, Nicholas J Wareham, Jytte Halkjaer, Anne Tjønneland, Kim Overvad, Marianne Uhre Jakobsen, Brian Buijsse, Annika Steffen, Domenico Palli, Giovanna Masala, Wim H M Saris, Thorkild I A Sørensen, and Edith J M Feskens

Subjects
Medicine, Science
Abstract

Experimental studies show that a reduction in dietary energy density (ED) is associated with reduced energy intake and body weight. However, few observational studies have investigated the role of ED on long-term weight and waist circumference change.This population-based prospective cohort study included 89,432 participants from five European countries with mean age 53 years (range: 20-78 years) at baseline and were followed for an average of 6.5 years (range: 1.9-12.5 years). Participants were free of cancer, cardiovascular diseases and diabetes at baseline. ED was calculated as the energy intake (kcal) from foods divided by the weight (g) of foods. Multiple linear regression analyses were performed to investigate the associations of ED with annual weight and waist circumference change. Mean ED was 1.7 kcal/g and differed across study centers. After adjusting for baseline anthropometrics, demographic and lifestyle factors, follow-up duration and energy from beverages, ED was not associated with weight change, but significantly associated with waist circumference change overall. For 1 kcal/g ED, the annual weight change was -42 g/year [95% confidence interval (CI): -112, 28] and annual waist circumference change was 0.09 cm/year [95% CI: 0.01, 0.18]. In participants with baseline BMI

Published
2009
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197. Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke : EPIC-CVD case-cohort study

Author

Ricci, Cristian, Wood, Angela, Muller, David, Gunter, Marc J, Agudo, Antonio, Boeing, Heiner, van der Schouw, Yvonne T, Warnakula, Samantha, Saieva, Calogero, Spijkerman, Annemieke, Sluijs, Ivonne, Tjønneland, Anne, Kyrø, Cecilie, Weiderpass, Elisabete, Kühn, Tilman, Kaaks, Rudolf, Sánchez, Maria-Jose, Panico, Salvatore, Agnoli, Claudia, Palli, Domenico, Tumino, Rosario, Engström, Gunnar, Melander, Olle, Bonnet, Fabrice, Boer, Jolanda M A, Key, Timothy J, Travis, Ruth C, Overvad, Kim, Verschuren, W M Monique, Quirós, J Ramón, Trichopoulou, Antonia, Papatesta, Eleni-Maria, Peppa, Eleni, Iribas, Conchi Moreno, Gavrila, Diana, Forslund, Ann-Sofie, Jansson, Jan-Håkan, Matullo, Giuseppe, Arriola, Larraitz, Freisling, Heinz, Lassale, Camille, Tzoulaki, Ioanna, Sharp, Stephen J, Forouhi, Nita G, Langenberg, Claudia, Saracci, Rodolfo, Sweeting, Michael, Brennan, Paul, Butterworth, Adam S, Riboli, Elio, Wareham, Nick J, Danesh, John, and Ferrari, Pietro

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