Author: "Kaakinen, Marika A." / Publisher: uppsala universitet, kardiovaskular epidemiologi - Searchworks@Jio Institute Digital Library Search Results

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26 results on '"Kaakinen, Marika A."'

1. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

Author: Scott, Robert A., Scott, Laura J., Maegi, Reedik, Marullo, Letizia, Gaulton, Kyle J., Kaakinen, Marika, Pervjakova, Natalia, Pers, Tune H., Johnson, Andrew D., Eicher, John D., Jackson, Anne U., Ferreira, Teresa, Lee, Yeji, Ma, Clement, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Qi, Lu, Van Zuydam, Natalie R., Mahajan, Anubha, Chen, Han, Almgren, Peter, Voight, Ben F., Grallert, Harald, Mueller-Nurasyid, Martina, Ried, Janina S., Rayner, Nigel W., Robertson, Neil, Karssen, Lennart C., Van Leeuwen, Elisabeth M., Willems, Sara M., Fuchsberger, Christian, Kwan, Phoenix, Teslovich, Tanya M., Chanda, Pritam, Li, Man, Lu, Yingchang, Dina, Christian, Thuillier, Dorothee, Yengo, Loic, Jiang, Longda, Sparso, Thomas, Kestler, Hans A., Chheda, Himanshu, Eisele, Lewin, Gustafsson, Stefan, Franberg, Mattias, Strawbridge, Rona J., Benediktsson, Rafn, Hreidarsson, Astradur B., Kong, Augustine, Sigurdsson, Gunnar, Kerrison, Nicola D., Luan, Jian'an, Liang, Liming, Meitinger, Thomas, Roden, Michael, Thorand, Barbara, Esko, Tonu, Mihailov, Evelin, Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Isomaa, Bo, Lyssenko, Valeriya, Tuomi, Tiinamaija, Couper, David J., Pankow, James S., Grarup, Niels, Have, Christian T., Jorgensen, Marit E., Jorgensen, Torben, Linneberg, Allan, Cornelis, Marilyn C., Van Dam, Rob M., Hunter, David J., Kraft, Peter, Sun, Qi, Edkins, Sarah, Owen, Katharine R., Perry, John R. B., Wood, Andrew R., Zeggini, Eleftheria, Tajes-Fernandes, Juan, Abecasis, Goncalo R., Bonnycastle, Lori L., Chines, Peter S., Stringham, Heather M., Koistinen, Heikki A., Kinnunen, Leena, Sennblad, Bengt, Muehleisen, Thomas W., Noethen, Markus M., Pechlivanis, Sonali, Baldassarre, Damiano, Gertow, Karl, Humphries, Steve E., Tremoli, Elena, Klopp, Norman, Meyer, Julia, Steinbach, Gerald, Wennauer, Roman, Eriksson, Johan G., Mannisto, Satu, Peltonen, Leena, Tikkanen, Emmi, Charpentier, Guillaume, Eury, Elodie, Lobbens, Stephane, Gigante, Bruna, Leander, Karin, McLeod, Olga, Bottinger, Erwin P., Gottesman, Omri, Ruderfer, Douglas, Blueher, Matthias, Kovacs, Peter, Tonjes, Anke, Maruthur, Nisa M., Scapoli, Chiara, Erbel, Raimund, Joeckel, Karl-Heinz, Moebus, Susanne, De Faire, Ulf, Hamsten, Anders, Stumvoll, Michael, Deloukas, Panagiotis, Donnelly, Peter J., Frayling, Timothy M., Hattersley, Andrew T., Ripatti, Samuli, Salomaa, Veikko, Pedersen, Nancy L., Boehm, Bernhard O., Bergman, Richard N., Collins, Francis S., Mohlke, Karen L., Tuomilehto, Jaakko, Hansen, Torben, Pedersen, Oluf, Barroso, Ines, Lannfelt, Lars, Ingelsson, Erik, Lind, Lars, Lindgren, Cecilia M., Cauchi, Stephane, Froguel, Philippe, Loos, Ruth J. F., Balkau, Beverley, Boeing, Heiner, Franks, Paul W., Gurrea, Aurelio Barricarte, Palli, Domenico, Van der Schouw, Yvonne T., Altshuler, David, Groop, Leif C., Langenberg, Claudia, Wareham, Nicholas J., Sijbrands, Eric, Van Duijn, Cornelia M., Florez, Jose C., Meigs, James B., Boerwinkle, Eric, Gieger, Christian, Strauch, Konstantin, Metspalu, Andres, Morris, Andrew D., Palmer, Colin N. A., Hu, Frank B., Thorsteinsdottir, Unnur, Stefansson, Kari, Dupuis, Josee, Morris, Andrew P., Boehnke, Michael, McCarthy, Mark I., Prokopenko, Inga, Scott, Robert A., Scott, Laura J., Maegi, Reedik, Marullo, Letizia, Gaulton, Kyle J., Kaakinen, Marika, Pervjakova, Natalia, Pers, Tune H., Johnson, Andrew D., Eicher, John D., Jackson, Anne U., Ferreira, Teresa, Lee, Yeji, Ma, Clement, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Qi, Lu, Van Zuydam, Natalie R., Mahajan, Anubha, Chen, Han, Almgren, Peter, Voight, Ben F., Grallert, Harald, Mueller-Nurasyid, Martina, Ried, Janina S., Rayner, Nigel W., Robertson, Neil, Karssen, Lennart C., Van Leeuwen, Elisabeth M., Willems, Sara M., Fuchsberger, Christian, Kwan, Phoenix, Teslovich, Tanya M., Chanda, Pritam, Li, Man, Lu, Yingchang, Dina, Christian, Thuillier, Dorothee, Yengo, Loic, Jiang, Longda, Sparso, Thomas, Kestler, Hans A., Chheda, Himanshu, Eisele, Lewin, Gustafsson, Stefan, Franberg, Mattias, Strawbridge, Rona J., Benediktsson, Rafn, Hreidarsson, Astradur B., Kong, Augustine, Sigurdsson, Gunnar, Kerrison, Nicola D., Luan, Jian'an, Liang, Liming, Meitinger, Thomas, Roden, Michael, Thorand, Barbara, Esko, Tonu, Mihailov, Evelin, Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Isomaa, Bo, Lyssenko, Valeriya, Tuomi, Tiinamaija, Couper, David J., Pankow, James S., Grarup, Niels, Have, Christian T., Jorgensen, Marit E., Jorgensen, Torben, Linneberg, Allan, Cornelis, Marilyn C., Van Dam, Rob M., Hunter, David J., Kraft, Peter, Sun, Qi, Edkins, Sarah, Owen, Katharine R., Perry, John R. B., Wood, Andrew R., Zeggini, Eleftheria, Tajes-Fernandes, Juan, Abecasis, Goncalo R., Bonnycastle, Lori L., Chines, Peter S., Stringham, Heather M., Koistinen, Heikki A., Kinnunen, Leena, Sennblad, Bengt, Muehleisen, Thomas W., Noethen, Markus M., Pechlivanis, Sonali, Baldassarre, Damiano, Gertow, Karl, Humphries, Steve E., Tremoli, Elena, Klopp, Norman, Meyer, Julia, Steinbach, Gerald, Wennauer, Roman, Eriksson, Johan G., Mannisto, Satu, Peltonen, Leena, Tikkanen, Emmi, Charpentier, Guillaume, Eury, Elodie, Lobbens, Stephane, Gigante, Bruna, Leander, Karin, McLeod, Olga, Bottinger, Erwin P., Gottesman, Omri, Ruderfer, Douglas, Blueher, Matthias, Kovacs, Peter, Tonjes, Anke, Maruthur, Nisa M., Scapoli, Chiara, Erbel, Raimund, Joeckel, Karl-Heinz, Moebus, Susanne, De Faire, Ulf, Hamsten, Anders, Stumvoll, Michael, Deloukas, Panagiotis, Donnelly, Peter J., Frayling, Timothy M., Hattersley, Andrew T., Ripatti, Samuli, Salomaa, Veikko, Pedersen, Nancy L., Boehm, Bernhard O., Bergman, Richard N., Collins, Francis S., Mohlke, Karen L., Tuomilehto, Jaakko, Hansen, Torben, Pedersen, Oluf, Barroso, Ines, Lannfelt, Lars, Ingelsson, Erik, Lind, Lars, Lindgren, Cecilia M., Cauchi, Stephane, Froguel, Philippe, Loos, Ruth J. F., Balkau, Beverley, Boeing, Heiner, Franks, Paul W., Gurrea, Aurelio Barricarte, Palli, Domenico, Van der Schouw, Yvonne T., Altshuler, David, Groop, Leif C., Langenberg, Claudia, Wareham, Nicholas J., Sijbrands, Eric, Van Duijn, Cornelia M., Florez, Jose C., Meigs, James B., Boerwinkle, Eric, Gieger, Christian, Strauch, Konstantin, Metspalu, Andres, Morris, Andrew D., Palmer, Colin N. A., Hu, Frank B., Thorsteinsdottir, Unnur, Stefansson, Kari, Dupuis, Josee, Morris, Andrew P., Boehnke, Michael, McCarthy, Mark I., and Prokopenko, Inga
Abstract: To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
Published: 2017
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2. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Ehret, Georg B., Ferreira, Teresa, Chasman, Daniel I., Jackson, Anne U., Schmidt, Ellen M., Johnson, Toby, Thorleifsson, Gudmar, Luan, Jian'an, Donnelly, Louise A., Kanoni, Stavroula, Petersen, Ann -Kristin, Pihurl, Vasyl, Strawbridge, Rona J., Shungin, Dmitry, Hughes, Maria F., Meirelles, Osorio, Kaakinen, Marika, Bouatia-Naji, Nabila, Kristiansson, Kati, Shah, Sonia, Kleber, Marcus E., Guo, Xiuqing, Lyytikainen, Leo-Pekka, Fava, Cristiano, Eriksson, Niclas, Nolte, Ilja M., Magnusson, Patrik K., Salfati, Elias L., Rallidis, Loukianos S., Theusch, Elizabeth, Smith, Andrew J. P., Folkersen, Lasse, Witkowska, Kate, Pers, Tune H., Joehanes, Roby, Kim, Stuart K., Lataniotis, Lazaros, Jansen, Rick, Johnson, Andrew D., Warren, Helen, Kim, Young Jin, Zhao, Wei, Wu, Ying, Tayo, Bamidele O., Bochud, Murielle, Absher, Devin, Adair, Linda S., Amin, Najaf, Arkingl, Dan E., Axelsson, Tomas, Baldassarre, Damian, Balkau, Beverley, Bandinelli, Stefania, Barnes, Michael R., Barroso, Ines, Bevan, Stephen, Bis, Joshua C., Bjornsdottir, Gyda, Boehnke, Michael, Boerwinkle, Eric, Bonnycastle, Lori L., Boomsma, Dorret I., Bornstein, Stefan R., Brown, Morris J., Burnier, Michel, Cabrera, Claudia P., Chambers, John C., Chang, I-Shou, Cheng, Ching-Yu, Chines, Peter S., Chung, Ren-Hua, Collins, Francis S., Connell, John M., Doring, Angela, Dallongeville, Jean, Danesh, John, de Faire, Ulf, Delgado, Graciela, Dominiczak, Anna F., Doney, Alex S. F., Drenos, Fotios, Edkins, Sarah, Eicher, John D., Elosua, Roberto, Enroth, Stefan, Erdmann, Jeanette, Eriksson, Per, Esko, Tonu, Evangelou, Evangelos, Evans, Alun, Fall, Tove, Farra, Martin, Felixl, Janine F., Ferrieres, Jean, Ferrucci, Luigi, Fornage, Myriam, Forrester, Terrence, Franceschinil, Nora, Franco, Oscar H., Franco-Cereceda, Anders, Fraser, Ross M., Ganesh, Santhi K., Gao, He, Gertow, Karl, Gianfagna, Francesco, Gigante, Bruna, Giulianini, Franco, Goe, Anuj, Goodall, Alison H., Goodarzi, Mark, Gorski, Mathias, Grassler, Jurgen, Groves, Christopher J., Gudnason, Vilmundur, Gyllensten, Ulf, Hallmans, Göran, Hartikainen, Anna-Liisa, Hassinen, Maija, Havulinna, Aki S., Hayward, Caroline, Hercberg, Serge, Herzig, Karl-Heinz, Hicks, Andrew A., Hingorani, Aroon D., Hirschhorn, Joel N., Hofmanl, Albert, Holmen, Jostein, Holmen, Oddgeir Lingaas, Hottenga, Jouke-Jan, Howard, Phil, Hsiung, Chao A., Hunt, Steven C., Ikram, M. Arfan, Illig, Thomas, Iribarren, Carlos, Jensen, Richard A., Kahonen, Mika, Kang, Hyun Min, Kathiresan, Sekar, Keating, Brendan J., Khaw, Kay-Tee, Kim, Yun Kyoung, Kim, Eric, Kivimaki, Mika, Klopp, Norman, Kolovou, Genovefa, Komulainen, Pirjo, Kooner, Jaspal S., Kosova, Gulum, Krauss, Ronald M., Kuh, Diana, Kutalik, Zoltan, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A., Lee, Nanette R., Lee, I-Te, Lee, Wen-Jane, Levy, Daniel, Li, Xiaohui, Liang, Kae-Woei, Lin, Honghuang, Lin, Li, Lindstrom, Jaana, Lobbens, Stephane, Mannisto, Satu, Muller, Gabriele, Muller-Nurasyid, Martina, Mach, Francois, Markus, Hugh S., Marouli, Eirini, McCarthy, Mark I., McKenzie, Colin A., Meneton, Pierre, Menni, Cristina, Metspalu, Andres, Mijatovic, Vladan, Moilanen, Leena, Montasser, May E., Morris, Andrew D., Morrison, Alanna C., Mulas, Antonella, Nagaraja, Ramaiah, Narisu, Narisu, Nikus, Kjell, O'Donnell, Christopher J., O'Reilly, Paul F., Ong, Ken K., Paccaud, Fred, Palmer, Cameron D., Parsa, Afshin, Pedersen, Nancy L., Penninx, Brenda W., Perola, Markus, Peters, Annette, Poulter, Neil, Pramstaller, Peter P., Psaty, Bruce M., Quertermous, Thomas, Rao, Dabeeru C., Rasheed, Asif, Rayner, N. William, Renstrom, Frida, Rettig, Rainer, Rice, Kenneth M., Roberts, Robert, Rose, Lynda M., Rossouw, Jacques, Samani, Nilesh J., Sanna, Serena, Saramies, Jouko, Schunkert, Heribert, Sebert, Sylvain, Sheu, Wayne H-H, Shin, Young-Ah, Sim, Xueling, Smit, Johannes H., Smith, Albert V., Sosa, Maria X., Spector, Tim D., Stancakova, Alena, Stanton, Alice V., Stirrups, Kathleen E., Stringham, Heather M., Sundström, Johan, Swift, Amy J., Syvänen, Ann-Christine, Tai, E-Shyong, Tanaka, Toshiko, Tarasov, Kirill V., Teumer, Alexander, Thorsteinsdottir, Unnur, Tobin, Martin D., Tremoli, Elena, Uitterlinden, Andre G., Uusitupa, Matti, Vaez, Ahmad, Vaidya, Dhananjay, van Duijn, Cornelia M., van Iperen, Erik P. A., Vasan, Ramachandran S., Verwoert, Germaine C., Virtamo, Jarmo, Vitart, Veronique, Voight, Benjamin F., Vollenweider, Peter, Wagner, Aline, Wain, Louise V., Wareham, Nicholas J., Watldns, Hugh, Weder, Alan B., Westra, Harm Jan, Wilks, Rainford, Wilsgaard, Tom, Wilson, James F., Wong, Tien Y., Yang, Tsun-Po, Yao, Jie, Yengo, Loic, Zhang, Weihua, Zhao, Jing Hua, Zhu, Xiaofeng, Bovet, Pascal, Cooper, Richard S., Mohlke, Karen L., Saleheen, Danish, Lee, Jong-Young, Elliott, Paul, Gierman, Hinco J., Willer, Cristen J., Franke, Lude, Hovingh, G. Kees, Taylor, Kent D., Dedoussis, George, Sever, Peter, Wong, Andrew, Lind, Lars, Assimes, Themistocles L., Njolstad, Inger, Schwarz, Peter E. H., Langenberg, Claudia, Snieder, Harold, Caulfield, Mark J., Melander, E., Laakso, Markku, Saltevo, Juha, Rauramaa, Rainer, Tuomilehto, Jaakko, Ingelsson, Erik, Lehtimaki, Terho, Hveem, Kristian, Palmas, Walter, Marz, Winfried, Kumar, Meena, Salomaa, Veikko, Chen, Yii-Der I., Rotter, Jerome I., Froguel, Philippe, Jarvelin, Marjo-Riitta, Lakatta, Edward G., Kuulasmaa, Kari, Franks, Paul W., Hamsten, Anders, Wichmann, H-Erich, Palmer, Colin N. A., Stefansson, Kari, Ridker, Paul M., Loos, Ruth J. F., Chalcravarti, Aravinda, Deloukas, Panos, Morris, Andrew P., Newton-Cheh, Christopher, Munroe, Patricia B., Ehret, Georg B., Ferreira, Teresa, Chasman, Daniel I., Jackson, Anne U., Schmidt, Ellen M., Johnson, Toby, Thorleifsson, Gudmar, Luan, Jian'an, Donnelly, Louise A., Kanoni, Stavroula, Petersen, Ann -Kristin, Pihurl, Vasyl, Strawbridge, Rona J., Shungin, Dmitry, Hughes, Maria F., Meirelles, Osorio, Kaakinen, Marika, Bouatia-Naji, Nabila, Kristiansson, Kati, Shah, Sonia, Kleber, Marcus E., Guo, Xiuqing, Lyytikainen, Leo-Pekka, Fava, Cristiano, Eriksson, Niclas, Nolte, Ilja M., Magnusson, Patrik K., Salfati, Elias L., Rallidis, Loukianos S., Theusch, Elizabeth, Smith, Andrew J. P., Folkersen, Lasse, Witkowska, Kate, Pers, Tune H., Joehanes, Roby, Kim, Stuart K., Lataniotis, Lazaros, Jansen, Rick, Johnson, Andrew D., Warren, Helen, Kim, Young Jin, Zhao, Wei, Wu, Ying, Tayo, Bamidele O., Bochud, Murielle, Absher, Devin, Adair, Linda S., Amin, Najaf, Arkingl, Dan E., Axelsson, Tomas, Baldassarre, Damian, Balkau, Beverley, Bandinelli, Stefania, Barnes, Michael R., Barroso, Ines, Bevan, Stephen, Bis, Joshua C., Bjornsdottir, Gyda, Boehnke, Michael, Boerwinkle, Eric, Bonnycastle, Lori L., Boomsma, Dorret I., Bornstein, Stefan R., Brown, Morris J., Burnier, Michel, Cabrera, Claudia P., Chambers, John C., Chang, I-Shou, Cheng, Ching-Yu, Chines, Peter S., Chung, Ren-Hua, Collins, Francis S., Connell, John M., Doring, Angela, Dallongeville, Jean, Danesh, John, de Faire, Ulf, Delgado, Graciela, Dominiczak, Anna F., Doney, Alex S. F., Drenos, Fotios, Edkins, Sarah, Eicher, John D., Elosua, Roberto, Enroth, Stefan, Erdmann, Jeanette, Eriksson, Per, Esko, Tonu, Evangelou, Evangelos, Evans, Alun, Fall, Tove, Farra, Martin, Felixl, Janine F., Ferrieres, Jean, Ferrucci, Luigi, Fornage, Myriam, Forrester, Terrence, Franceschinil, Nora, Franco, Oscar H., Franco-Cereceda, Anders, Fraser, Ross M., Ganesh, Santhi K., Gao, He, Gertow, Karl, Gianfagna, Francesco, Gigante, Bruna, Giulianini, Franco, Goe, Anuj, Goodall, Alison H., Goodarzi, Mark, Gorski, Mathias, Grassler, Jurgen, Groves, Christopher J., Gudnason, Vilmundur, Gyllensten, Ulf, Hallmans, Göran, Hartikainen, Anna-Liisa, Hassinen, Maija, Havulinna, Aki S., Hayward, Caroline, Hercberg, Serge, Herzig, Karl-Heinz, Hicks, Andrew A., Hingorani, Aroon D., Hirschhorn, Joel N., Hofmanl, Albert, Holmen, Jostein, Holmen, Oddgeir Lingaas, Hottenga, Jouke-Jan, Howard, Phil, Hsiung, Chao A., Hunt, Steven C., Ikram, M. Arfan, Illig, Thomas, Iribarren, Carlos, Jensen, Richard A., Kahonen, Mika, Kang, Hyun Min, Kathiresan, Sekar, Keating, Brendan J., Khaw, Kay-Tee, Kim, Yun Kyoung, Kim, Eric, Kivimaki, Mika, Klopp, Norman, Kolovou, Genovefa, Komulainen, Pirjo, Kooner, Jaspal S., Kosova, Gulum, Krauss, Ronald M., Kuh, Diana, Kutalik, Zoltan, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A., Lee, Nanette R., Lee, I-Te, Lee, Wen-Jane, Levy, Daniel, Li, Xiaohui, Liang, Kae-Woei, Lin, Honghuang, Lin, Li, Lindstrom, Jaana, Lobbens, Stephane, Mannisto, Satu, Muller, Gabriele, Muller-Nurasyid, Martina, Mach, Francois, Markus, Hugh S., Marouli, Eirini, McCarthy, Mark I., McKenzie, Colin A., Meneton, Pierre, Menni, Cristina, Metspalu, Andres, Mijatovic, Vladan, Moilanen, Leena, Montasser, May E., Morris, Andrew D., Morrison, Alanna C., Mulas, Antonella, Nagaraja, Ramaiah, Narisu, Narisu, Nikus, Kjell, O'Donnell, Christopher J., O'Reilly, Paul F., Ong, Ken K., Paccaud, Fred, Palmer, Cameron D., Parsa, Afshin, Pedersen, Nancy L., Penninx, Brenda W., Perola, Markus, Peters, Annette, Poulter, Neil, Pramstaller, Peter P., Psaty, Bruce M., Quertermous, Thomas, Rao, Dabeeru C., Rasheed, Asif, Rayner, N. William, Renstrom, Frida, Rettig, Rainer, Rice, Kenneth M., Roberts, Robert, Rose, Lynda M., Rossouw, Jacques, Samani, Nilesh J., Sanna, Serena, Saramies, Jouko, Schunkert, Heribert, Sebert, Sylvain, Sheu, Wayne H-H, Shin, Young-Ah, Sim, Xueling, Smit, Johannes H., Smith, Albert V., Sosa, Maria X., Spector, Tim D., Stancakova, Alena, Stanton, Alice V., Stirrups, Kathleen E., Stringham, Heather M., Sundström, Johan, Swift, Amy J., Syvänen, Ann-Christine, Tai, E-Shyong, Tanaka, Toshiko, Tarasov, Kirill V., Teumer, Alexander, Thorsteinsdottir, Unnur, Tobin, Martin D., Tremoli, Elena, Uitterlinden, Andre G., Uusitupa, Matti, Vaez, Ahmad, Vaidya, Dhananjay, van Duijn, Cornelia M., van Iperen, Erik P. A., Vasan, Ramachandran S., Verwoert, Germaine C., Virtamo, Jarmo, Vitart, Veronique, Voight, Benjamin F., Vollenweider, Peter, Wagner, Aline, Wain, Louise V., Wareham, Nicholas J., Watldns, Hugh, Weder, Alan B., Westra, Harm Jan, Wilks, Rainford, Wilsgaard, Tom, Wilson, James F., Wong, Tien Y., Yang, Tsun-Po, Yao, Jie, Yengo, Loic, Zhang, Weihua, Zhao, Jing Hua, Zhu, Xiaofeng, Bovet, Pascal, Cooper, Richard S., Mohlke, Karen L., Saleheen, Danish, Lee, Jong-Young, Elliott, Paul, Gierman, Hinco J., Willer, Cristen J., Franke, Lude, Hovingh, G. Kees, Taylor, Kent D., Dedoussis, George, Sever, Peter, Wong, Andrew, Lind, Lars, Assimes, Themistocles L., Njolstad, Inger, Schwarz, Peter E. H., Langenberg, Claudia, Snieder, Harold, Caulfield, Mark J., Melander, E., Laakso, Markku, Saltevo, Juha, Rauramaa, Rainer, Tuomilehto, Jaakko, Ingelsson, Erik, Lehtimaki, Terho, Hveem, Kristian, Palmas, Walter, Marz, Winfried, Kumar, Meena, Salomaa, Veikko, Chen, Yii-Der I., Rotter, Jerome I., Froguel, Philippe, Jarvelin, Marjo-Riitta, Lakatta, Edward G., Kuulasmaa, Kari, Franks, Paul W., Hamsten, Anders, Wichmann, H-Erich, Palmer, Colin N. A., Stefansson, Kari, Ridker, Paul M., Loos, Ruth J. F., Chalcravarti, Aravinda, Deloukas, Panos, Morris, Andrew P., Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Published: 2016
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3. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Author: Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, Loos, Ruth J. F., Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, and Loos, Ruth J. F.
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 similar 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< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap, Correction in: PLOS Genetics, Vol. 12, nr 6, s. e1006166DOI: 10.1371/journal.pgen.1006166
Published: 2015
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4. Adiposity as a cause of cardiovascular disease : a Mendelian randomization study

Author: Hägg, Sara, Fall, Tove, Ploner, Alexander, Maegi, Reedik, Fischer, Krista, Draisma, Harmen H. M., Kals, Mart, de Vries, Paul S., Dehghan, Abbas, Willems, Sara M., Sarin, Antti-Pekka, Kristiansson, Kati, Nuotio, Marja-Liisa, Havulinna, Aki S., de Bruijn, Renee F. A. G., Ikram, M. Arfan, Kuningas, Maris, Stricker, Bruno H., Franco, Oscar H., Benyamin, Beben, Gieger, Christian, Hall, Alistair S., Huikari, Ville, Jula, Antti, Jarvelin, Marjo-Riitta, Kaakinen, Marika, Kaprio, Jaakko, Kobl, Michael, Mangino, Massimo, Nelson, Christopher P., Palotie, Aarno, Samani, Nilesh J., Spector, Tim D., Strachan, David P., Tobin, Martin D., Whitfield, John B., Uitterlinden, Andre G., Salomaa, Veikko, Syvänen, Ann-Christine, Kuulasmaa, Kari, Magnusson, Patrik K., Esko, Tonu, Hofman, Albert, de Geus, Eco J. C., Lind, Lars, Giedraitis, Vilmantas, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Gianfagna, Francesco, Brambilla, Paolo, Ripatti, Samuli, van Duijn, Cornelia M., Metspalu, Andres, Prokopenko, Inga, McCarthy, Mark I., Pedersen, Nancy L., Ingelsson, Erik, Hägg, Sara, Fall, Tove, Ploner, Alexander, Maegi, Reedik, Fischer, Krista, Draisma, Harmen H. M., Kals, Mart, de Vries, Paul S., Dehghan, Abbas, Willems, Sara M., Sarin, Antti-Pekka, Kristiansson, Kati, Nuotio, Marja-Liisa, Havulinna, Aki S., de Bruijn, Renee F. A. G., Ikram, M. Arfan, Kuningas, Maris, Stricker, Bruno H., Franco, Oscar H., Benyamin, Beben, Gieger, Christian, Hall, Alistair S., Huikari, Ville, Jula, Antti, Jarvelin, Marjo-Riitta, Kaakinen, Marika, Kaprio, Jaakko, Kobl, Michael, Mangino, Massimo, Nelson, Christopher P., Palotie, Aarno, Samani, Nilesh J., Spector, Tim D., Strachan, David P., Tobin, Martin D., Whitfield, John B., Uitterlinden, Andre G., Salomaa, Veikko, Syvänen, Ann-Christine, Kuulasmaa, Kari, Magnusson, Patrik K., Esko, Tonu, Hofman, Albert, de Geus, Eco J. C., Lind, Lars, Giedraitis, Vilmantas, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Gianfagna, Francesco, Brambilla, Paolo, Ripatti, Samuli, van Duijn, Cornelia M., Metspalu, Andres, Prokopenko, Inga, McCarthy, Mark I., Pedersen, Nancy L., and Ingelsson, Erik
Abstract: Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9.10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (beta = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3.10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke., De två första författarna delar förstaförfattarskapet.
Published: 2015
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5. Age- and sex-specific causal effects of adiposity on cardiovascular risk factors

Author: Fall, Tove, Hägg, Sara, Ploner, Alexander, Mägi, Reedik, Fischer, Krista, Draisma, Harmen H M, Sarin, Antti-Pekka, Benyamin, Beben, Ladenvall, Claes, Åkerlund, Mikael, Kals, Mart, Esko, Tõnu, Nelson, Christopher P, Kaakinen, Marika, Huikari, Ville, Mangino, Massimo, Meirhaeghe, Aline, Kristiansson, Kati, Nuotio, Marja-Liisa, Kobl, Michael, Grallert, Harald, Dehghan, Abbas, Kuningas, Maris, de Vries, Paul S, de Bruijn, Renée F A G, Willems, Sara M, Heikkilä, Kauko, Silventoinen, Karri, Pietiläinen, Kirsi H, Legry, Vanessa, Giedraitis, Vilmantas, Goumidi, Louisa, Syvänen, Ann-Christine, Strauch, Konstantin, Koenig, Wolfgang, Lichtner, Peter, Herder, Christian, Palotie, Aarno, Menni, Cristina, Uitterlinden, André G, Kuulasmaa, Kari, Havulinna, Aki S, Moreno, Luis A, Gonzalez-Gross, Marcela, Evans, Alun, Tregouet, David-Alexandre, Yarnell, John W G, Virtamo, Jarmo, Ferrières, Jean, Veronesi, Giovanni, Perola, Markus, Arveiler, Dominique, Brambilla, Paolo, Lind, Lars, Kaprio, Jaakko, Hofman, Albert, Stricker, Bruno H, van Duijn, Cornelia M, Ikram, M Arfan, Franco, Oscar H, Cottel, Dominique, Dallongeville, Jean, Hall, Alistair S, Jula, Antti, Tobin, Martin D, Penninx, Brenda W, Peters, Annette, Gieger, Christian, Samani, Nilesh J, Montgomery, Grant W, Whitfield, John B, Martin, Nicholas G, Groop, Leif, Spector, Tim D, Magnusson, Patrik K, Amouyel, Philippe, Boomsma, Dorret I, Nilsson, Peter M, Järvelin, Marjo-Riitta, Lyssenko, Valeriya, Metspalu, Andres, Strachan, David P, Salomaa, Veikko, Ripatti, Samuli, Pedersen, Nancy L, Prokopenko, Inga, McCarthy, Mark I, Ingelsson, Erik, Fall, Tove, Hägg, Sara, Ploner, Alexander, Mägi, Reedik, Fischer, Krista, Draisma, Harmen H M, Sarin, Antti-Pekka, Benyamin, Beben, Ladenvall, Claes, Åkerlund, Mikael, Kals, Mart, Esko, Tõnu, Nelson, Christopher P, Kaakinen, Marika, Huikari, Ville, Mangino, Massimo, Meirhaeghe, Aline, Kristiansson, Kati, Nuotio, Marja-Liisa, Kobl, Michael, Grallert, Harald, Dehghan, Abbas, Kuningas, Maris, de Vries, Paul S, de Bruijn, Renée F A G, Willems, Sara M, Heikkilä, Kauko, Silventoinen, Karri, Pietiläinen, Kirsi H, Legry, Vanessa, Giedraitis, Vilmantas, Goumidi, Louisa, Syvänen, Ann-Christine, Strauch, Konstantin, Koenig, Wolfgang, Lichtner, Peter, Herder, Christian, Palotie, Aarno, Menni, Cristina, Uitterlinden, André G, Kuulasmaa, Kari, Havulinna, Aki S, Moreno, Luis A, Gonzalez-Gross, Marcela, Evans, Alun, Tregouet, David-Alexandre, Yarnell, John W G, Virtamo, Jarmo, Ferrières, Jean, Veronesi, Giovanni, Perola, Markus, Arveiler, Dominique, Brambilla, Paolo, Lind, Lars, Kaprio, Jaakko, Hofman, Albert, Stricker, Bruno H, van Duijn, Cornelia M, Ikram, M Arfan, Franco, Oscar H, Cottel, Dominique, Dallongeville, Jean, Hall, Alistair S, Jula, Antti, Tobin, Martin D, Penninx, Brenda W, Peters, Annette, Gieger, Christian, Samani, Nilesh J, Montgomery, Grant W, Whitfield, John B, Martin, Nicholas G, Groop, Leif, Spector, Tim D, Magnusson, Patrik K, Amouyel, Philippe, Boomsma, Dorret I, Nilsson, Peter M, Järvelin, Marjo-Riitta, Lyssenko, Valeriya, Metspalu, Andres, Strachan, David P, Salomaa, Veikko, Ripatti, Samuli, Pedersen, Nancy L, Prokopenko, Inga, McCarthy, Mark I, and Ingelsson, Erik
Abstract: Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors., T.V. and S.H. contributed equally to this work.
Published: 2015
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6. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Author: Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, Loos, Ruth J. F., Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, and Loos, Ruth J. F.
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 similar 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< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap, Correction in: PLOS Genetics, Vol. 12, nr 6, s. e1006166DOI: 10.1371/journal.pgen.1006166
Published: 2015
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7. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Author: Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, Loos, Ruth J. F., Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, and Loos, Ruth J. F.
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 similar 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< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap, Funding:Funding for this study was provided by the Aarne Koskelo Foundation; the Aase and Ejner Danielsens Foundation; the Academy of Finland (40758, 41071, 77299, 102318, 104781, 117787, 117844, 118590, 120315, 121584, 123885, 124243, 124282, 126925, 129269, 129293, 129378, 130326, 134309, 134791, 136895, 139635, 211497, 263836, 263924, 1114194, 24300796); the Agency for Health Care Policy Research (HS06516); the Agency for Science, Technology and Research of Singapore (A*STAR); the Ahokas Foundation; the ALF/LUA research grant in Gothenburg; the ALK-Abello A/S (Horsholm, Denmark), Timber Merchant Vilhelm Bangs Foundation, MEKOS Laboratories Denmark; the Althingi (the Icelandic Parliament); the American Heart Association (AHA; 13POST16500011); the ANR ("Agence Nationale de la 359 Recherche"); the Ark (NHMRC Enabling Facility); the Arthritis Research UK (19542, 18030); the AstraZeneca; the Augustinus Foundation; the Australian National Health and Medical Research Council (NHMRC; 241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672, 613601 and 1011506); the Australian Research Council (ARC; DP0770096 and DP1093502); the Becket Foundation; the bi-national BMBF/ANR funded project CARDomics (01KU0908A); the Biobanking and Biomolecular Resources Research Infrastructure (BBMRINL; 184.021.007, CP 32); the Biocentrum Helsinki; the Boehringer Ingelheim Foundation; the British Heart Foundation (RG/10/12/28456, SP/04/ 002); the Canadian Institutes for Health Reseaerch (FRCN-CCT-83028); the Cancer Research UK (C490/A10124, C490/A10119); the Center for Medical Systems Biology (CMSB; NWO Genomics); the Centers for Disease Control and Prevention and Association of Schools of Public Health (1734, S043, S3486); the Centre of Excellence Baden-Wurttemberg Metabolic Disorders; the Chief Scientist Office of the Scottish Government; the Clinical Research Facility at Guys & St Thomas NHS Foundation Trust; the Contrat de Projets Etat-Region (
Published: 2015
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8. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Author: Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, Loos, Ruth J. F., Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, and Loos, Ruth J. F.
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 similar 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< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap, Correction in: PLOS Genetics, Vol. 12, nr 6, s. e1006166DOI: 10.1371/journal.pgen.1006166
Published: 2015
Full Text: View/download PDF

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

Author: Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, Loos, Ruth J. F., Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tonu, Fall, Tove, Kilpelainen, Tuomas O., Lu, Yingchang, Magi, Reedik, Mihailov, Evelin, Pers, Tune H., Rueeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amelie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Mueller, Gabriele, Mueller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renstrom, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stancakova, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W., van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loic, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blueher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S., Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Graessler, Juergen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G., Hui, Jennie, Husemoen, Lise L., Hutri-Kahonen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jorgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krueger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindstrom, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stephane, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Perusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparso, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Toenjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Voelker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Boeger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Gronberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliovaara, Markku, Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kaehoenen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G., Laakso, Markku, Lakka, Timo A., Lehtimaki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mantyselka, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J., Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Verbeek, Andre L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Voelzke, Henry, Vollenweider, Peter, Waeber, Gerard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltan, and Loos, Ruth J. F.
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 similar 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< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap, Funding:Funding for this study was provided by the Aarne Koskelo Foundation; the Aase and Ejner Danielsens Foundation; the Academy of Finland (40758, 41071, 77299, 102318, 104781, 117787, 117844, 118590, 120315, 121584, 123885, 124243, 124282, 126925, 129269, 129293, 129378, 130326, 134309, 134791, 136895, 139635, 211497, 263836, 263924, 1114194, 24300796); the Agency for Health Care Policy Research (HS06516); the Agency for Science, Technology and Research of Singapore (A*STAR); the Ahokas Foundation; the ALF/LUA research grant in Gothenburg; the ALK-Abello A/S (Horsholm, Denmark), Timber Merchant Vilhelm Bangs Foundation, MEKOS Laboratories Denmark; the Althingi (the Icelandic Parliament); the American Heart Association (AHA; 13POST16500011); the ANR ("Agence Nationale de la 359 Recherche"); the Ark (NHMRC Enabling Facility); the Arthritis Research UK (19542, 18030); the AstraZeneca; the Augustinus Foundation; the Australian National Health and Medical Research Council (NHMRC; 241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672, 613601 and 1011506); the Australian Research Council (ARC; DP0770096 and DP1093502); the Becket Foundation; the bi-national BMBF/ANR funded project CARDomics (01KU0908A); the Biobanking and Biomolecular Resources Research Infrastructure (BBMRINL; 184.021.007, CP 32); the Biocentrum Helsinki; the Boehringer Ingelheim Foundation; the British Heart Foundation (RG/10/12/28456, SP/04/ 002); the Canadian Institutes for Health Reseaerch (FRCN-CCT-83028); the Cancer Research UK (C490/A10124, C490/A10119); the Center for Medical Systems Biology (CMSB; NWO Genomics); the Centers for Disease Control and Prevention and Association of Schools of Public Health (1734, S043, S3486); the Centre of Excellence Baden-Wurttemberg Metabolic Disorders; the Chief Scientist Office of the Scottish Government; the Clinical Research Facility at Guys & St Thomas NHS Foundation Trust; the Contrat de Projets Etat-Region (
Published: 2015
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10. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

Author: Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, Walker, Brian R., Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, and Walker, Brian R.
Abstract: Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding alpha 1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
Published: 2014
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11. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

Author: Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, Walker, Brian R., Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, and Walker, Brian R.
Abstract: Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding alpha 1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
Published: 2014
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12. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

Author: Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, Walker, Brian R., Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, and Walker, Brian R.
Abstract: Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding alpha 1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
Published: 2014
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13. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

Author: Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, Walker, Brian R., Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, and Walker, Brian R.
Abstract: Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding alpha 1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
Published: 2014
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14. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

Author: Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, Walker, Brian R., Bolton, Jennifer L., Hayward, Caroline, Direk, Nese, Lewis, John G., Hammond, Geoffrey L., Hill, Lesley A., Anderson, Anna, Huffman, Jennifer, Wilson, James F., Campbell, Harry, Rudan, Igor, Wright, Alan, Hastie, Nicholas, Wild, Sarah H., Velders, Fleur P., Hofman, Albert, Uitterlinden, Andre G., Lahti, Jari, Raikkonen, Katri, Kajantie, Eero, Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Kaakinen, Marika, Jarvelin, Marjo-Riitta, Timpson, Nicholas J., Smith, George Davey, Ring, Susan M., Evans, David M., St Pourcain, Beate, Tanaka, Toshiko, Milaneschi, Yuri, Bandinelli, Stefania, Ferrucci, Luigi, van der Harst, Pim, Rosmalen, Judith G. M., Bakker, Stephen J. L., Verweij, Niek, Dullaart, Robin P. F., Mahajan, Anubha, Lindgren, Cecilia M., Morris, Andrew, Lind, Lars, Ingelsson, Erik, Anderson, Laura N., Pennell, Craig E., Lye, Stephen J., Matthews, Stephen G., Eriksson, Joel, Mellstrom, Dan, Ohlsson, Claes, Price, Jackie F., Strachan, Mark W. J., Reynolds, Rebecca M., Tiemeier, Henning, and Walker, Brian R.
Abstract: Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding alpha 1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
Published: 2014
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15. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

Author: Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., Hyppoenen, Elina, Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., and Hyppoenen, Elina
Abstract: Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH) D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH) D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH) D (p = 6.52x10(-27)). The BMI allele score was associated both with BMI (p = 6.30x10(-62)) and 25(OH) D (20.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH) D (p <= 8.07x10(-57) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH) D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH) D with BMI, a finding that was confirmed using data from the GIANT consortium (p >= 0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH) D, while any effects of lower 25(OH) D increasing BMI are likely to be small. Populati
Published: 2013
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16. Common variants associated with plasma triglycerides and risk for coronary artery disease

Author: Do, Ron, Willer, Cristen J., Schmidt, Ellen M., Sengupta, Sebanti, Gao, Chi, Peloso, Gina M., Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L., Mora, Samia, Beckmann, Jacques S., Bragg-Gresham, Jennifer L., Chang, Hsing-Yi, Demirkan, Ayse, Den Hertog, Heleen M., Donnelly, Louise A., Ehret, Georg B., Esko, Tonu, Feitosa, Mary F., Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Fraser, Ross M., Freitag, Daniel F., Gurdasani, Deepti, Heikkila, Kauko, Hyppoenen, Elina, Isaacs, Aaron, Jackson, Anne U., Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E., Li, Xiaohui, Luan, Jian'an, Lyytikainen, Leo-Pekka, Magnusson, Patrik K. E., Mangino, Massimo, Mihailov, Evelin, Montasser, May E., Mueller-Nurasyid, Martina, Nolte, Ilja M., O'Connell, Jeffrey R., Palmer, Cameron D., Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K., Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J., Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M., Thorleifsson, Gudmar, Van den Herik, Evita G., Voight, Benjamin F., Volcik, Kelly A., Waite, Lindsay L., Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Ines, Been, Latonya F., Bolton, Jennifer L., Bonnycastle, Lori L., Brambilla, Paolo, Burnett, Mary S., Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S. F., Doering, Angela, Elliott, Paul, Epstein, Stephen E., Eyjolfsson, Gudmundur Ingi, Gigante, Bruna, Goodarzi, Mark O., Grallert, Harald, Gravito, Martha L., Groves, Christopher J., Hallmans, Goran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A., Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R., Kaleebu, Pontiano, Kastelein, John J. P., Khaw, Kay-Tee, Kim, Eric, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J. F., Mach, Francois, McArdle, Wendy L., Meisinger, Christa, Mitchell, Braxton D., Mueller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V. M., Nsubuga, Rebecca N., Olafsson, Isleifur, Ong, Ken K., Palotie, Aarno, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J., Reilly, Muredach P., Ridker, Paul M., Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stancakova, Alena, Stirrups, Kathleen, Swift, Amy J., Tiret, Laurence, Uitterlinden, Andre G., van Pelt, L. Joost, Vedantam, Sailaja, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F., Young, Elizabeth H., Zhao, Jing Hua, Adair, Linda S., Arveiler, Dominique, Assimes, Themistocles L., Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O., Boomsma, Dorret I., Borecki, Ingrid B., Bornstein, Stefan R., Bovet, Pascal, Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C., Chen, Yii-Der Ida, Collins, Francis S., Cooper, Richard S., Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B., Ferrieres, Jean, Ferrucci, Luigi, Freimer, Nelson B., Gieger, Christian, Groop, Leif C., Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Hingorani, Aroon, Hirschhorn, Joel N., Hofman, Albert, Hovingh, G. Kees, Hsiung, Chao Agnes, Humphries, Steve E., Hunt, Steven C., Hveem, Kristian, Iribarren, Carlos, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kaprio, Jaakko, Kesaniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S., Koudstaal, Peter J., Krauss, Ronald M., Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O., Laakso, Markku, Lakka, Timo A., Lind, Lars, Lindgren, Cecilia M., Martin, Nicholas G., Maerz, Winfried, McCarthy, Mark I., McKenzie, Colin A., Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D., Munroe, Patricia B., Njolstad, Inger, Pedersen, Nancy L., Power, Chris, Pramstaller, Peter P., Price, Jackie F., Psaty, Bruce M., Quertermous, Thomas, Rauramaa, Rainer, Saleheen, Danish, Salomaa, Veikko, Sanghera, Dharambir K., Saramies, Jouko, Schwarz, Peter E. H., Sheu, Wayne H-H, Shuldiner, Alan R., Siegbahn, Agneta, Spector, Tim D., Stefansson, Kari, Strachan, David P., Tayo, Bamidele O., Tremoli, Elena, Tuomilehto, Jaakko, Uusitupa, Matti, van Duijn, Cornelia M., Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J., Whitfield, John B., Wolffenbuttel, Bruce H. R., Altshuler, David, Ordovas, Jose M., Boerwinkle, Eric, Palmer, Colin N. A., Thorsteinsdottir, Unnur, Chasman, Daniel I., Rotter, Jerome I., Franks, Paul W., Ripatti, Samuli, Cupples, L. Adrienne, Sandhu, Manjinder S., Rich, Stephen S., Boehnke, Michael, Deloukas, Panos, Mohlke, Karen L., Ingelsson, Erik, Abecasis, Goncalo R., Daly, Mark J., Neale, Benjamin M., Kathiresan, Sekar, Do, Ron, Willer, Cristen J., Schmidt, Ellen M., Sengupta, Sebanti, Gao, Chi, Peloso, Gina M., Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L., Mora, Samia, Beckmann, Jacques S., Bragg-Gresham, Jennifer L., Chang, Hsing-Yi, Demirkan, Ayse, Den Hertog, Heleen M., Donnelly, Louise A., Ehret, Georg B., Esko, Tonu, Feitosa, Mary F., Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Fraser, Ross M., Freitag, Daniel F., Gurdasani, Deepti, Heikkila, Kauko, Hyppoenen, Elina, Isaacs, Aaron, Jackson, Anne U., Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E., Li, Xiaohui, Luan, Jian'an, Lyytikainen, Leo-Pekka, Magnusson, Patrik K. E., Mangino, Massimo, Mihailov, Evelin, Montasser, May E., Mueller-Nurasyid, Martina, Nolte, Ilja M., O'Connell, Jeffrey R., Palmer, Cameron D., Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K., Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J., Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M., Thorleifsson, Gudmar, Van den Herik, Evita G., Voight, Benjamin F., Volcik, Kelly A., Waite, Lindsay L., Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Ines, Been, Latonya F., Bolton, Jennifer L., Bonnycastle, Lori L., Brambilla, Paolo, Burnett, Mary S., Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S. F., Doering, Angela, Elliott, Paul, Epstein, Stephen E., Eyjolfsson, Gudmundur Ingi, Gigante, Bruna, Goodarzi, Mark O., Grallert, Harald, Gravito, Martha L., Groves, Christopher J., Hallmans, Goran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A., Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R., Kaleebu, Pontiano, Kastelein, John J. P., Khaw, Kay-Tee, Kim, Eric, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J. F., Mach, Francois, McArdle, Wendy L., Meisinger, Christa, Mitchell, Braxton D., Mueller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V. M., Nsubuga, Rebecca N., Olafsson, Isleifur, Ong, Ken K., Palotie, Aarno, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J., Reilly, Muredach P., Ridker, Paul M., Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stancakova, Alena, Stirrups, Kathleen, Swift, Amy J., Tiret, Laurence, Uitterlinden, Andre G., van Pelt, L. Joost, Vedantam, Sailaja, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F., Young, Elizabeth H., Zhao, Jing Hua, Adair, Linda S., Arveiler, Dominique, Assimes, Themistocles L., Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O., Boomsma, Dorret I., Borecki, Ingrid B., Bornstein, Stefan R., Bovet, Pascal, Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C., Chen, Yii-Der Ida, Collins, Francis S., Cooper, Richard S., Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B., Ferrieres, Jean, Ferrucci, Luigi, Freimer, Nelson B., Gieger, Christian, Groop, Leif C., Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Hingorani, Aroon, Hirschhorn, Joel N., Hofman, Albert, Hovingh, G. Kees, Hsiung, Chao Agnes, Humphries, Steve E., Hunt, Steven C., Hveem, Kristian, Iribarren, Carlos, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kaprio, Jaakko, Kesaniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S., Koudstaal, Peter J., Krauss, Ronald M., Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O., Laakso, Markku, Lakka, Timo A., Lind, Lars, Lindgren, Cecilia M., Martin, Nicholas G., Maerz, Winfried, McCarthy, Mark I., McKenzie, Colin A., Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D., Munroe, Patricia B., Njolstad, Inger, Pedersen, Nancy L., Power, Chris, Pramstaller, Peter P., Price, Jackie F., Psaty, Bruce M., Quertermous, Thomas, Rauramaa, Rainer, Saleheen, Danish, Salomaa, Veikko, Sanghera, Dharambir K., Saramies, Jouko, Schwarz, Peter E. H., Sheu, Wayne H-H, Shuldiner, Alan R., Siegbahn, Agneta, Spector, Tim D., Stefansson, Kari, Strachan, David P., Tayo, Bamidele O., Tremoli, Elena, Tuomilehto, Jaakko, Uusitupa, Matti, van Duijn, Cornelia M., Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J., Whitfield, John B., Wolffenbuttel, Bruce H. R., Altshuler, David, Ordovas, Jose M., Boerwinkle, Eric, Palmer, Colin N. A., Thorsteinsdottir, Unnur, Chasman, Daniel I., Rotter, Jerome I., Franks, Paul W., Ripatti, Samuli, Cupples, L. Adrienne, Sandhu, Manjinder S., Rich, Stephen S., Boehnke, Michael, Deloukas, Panos, Mohlke, Karen L., Ingelsson, Erik, Abecasis, Goncalo R., Daly, Mark J., Neale, Benjamin M., and Kathiresan, Sekar
Abstract: Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
Published: 2013
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17. Discovery and refinement of loci associated with lipid levels

Author: Willer, Cristen J., Schmidt, Ellen M., Sengupta, Sebanti, Peloso, Gina M., Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L., Mora, Samia, Beckmann, Jacques S., Bragg-Gresham, Jennifer L., Chang, Hsing-Yi, Demirkan, Ayse, Den Hertog, Heleen M., Do, Ron, Donnelly, Louise A., Ehret, Georg B., Esko, Tonu, Feitosa, Mary F., Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Fraser, Ross M., Freitag, Daniel F., Gurdasani, Deepti, Heikkila, Kauko, Hyppoenen, Elina, Isaacs, Aaron, Jackson, Anne U., Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E., Li, Xiaohui, Luan, Jian'an, Lyytikainen, Leo-Pekka, Magnusson, Patrik K. E., Mangino, Massimo, Mihailov, Evelin, Montasser, May E., Mueller-Nurasyid, Martina, Nolte, Ilja M., O'Connell, Jeffrey R., Palmer, Cameron D., Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K., Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J., Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M., Thorleifsson, Gudmar, Van den Herik, Evita G., Voight, Benjamin F., Volcik, Kelly A., Waite, Lindsay L., Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Ines, Been, Latonya F., Bolton, Jennifer L., Bonnycastle, Lori L., Brambilla, Paolo, Burnett, Mary S., Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S. F., Doering, Angela, Elliott, Paul, Epstein, Stephen E., Eyjolfsson, Gudmundur Ingi, Gigante, Bruna, Goodarzi, Mark O., Grallert, Harald, Gravito, Martha L., Groves, Christopher J., Hallmans, Goran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A., Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R., Kaleebu, Pontiano, Kastelein, John J. P., Khaw, Kay-Tee, Kim, Eric, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J. F., Mach, Francois, McArdle, Wendy L., Meisinger, Christa, Mitchell, Braxton D., Mueller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V. M., Nsubuga, Rebecca N., Olafsson, Isleifur, Ong, Ken K., Palotie, Aarno, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J., Reilly, Muredach P., Ridker, Paul M., Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stancakova, Alena, Stirrups, Kathleen, Swift, Amy J., Tiret, Laurence, Uitterlinden, Andre G., van Pelt, L. Joost, Vedantam, Sailaja, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F., Young, Elizabeth H., Zhao, Jing Hua, Adair, Linda S., Arveiler, Dominique, Assimes, Themistocles L., Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O., Boomsma, Dorret I., Borecki, Ingrid B., Bornstein, Stefan R., Bovet, Pascal, Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C., Chen, Yii-Der Ida, Collins, Francis S., Cooper, Richard S., Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B., Ferrieres, Jean, Ferrucci, Luigi, Freimer, Nelson B., Gieger, Christian, Groop, Leif C., Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Hingorani, Aroon, Hirschhorn, Joel N., Hofman, Albert, Hovingh, G. Kees, Hsiung, Chao Agnes, Humphries, Steve E., Hunt, Steven C., Hveem, Kristian, Iribarren, Carlos, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kaprio, Jaakko, Kesaniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S., Koudstaal, Peter J., Krauss, Ronald M., Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O., Laakso, Markku, Lakka, Timo A., Lind, Lars, Lindgren, Cecilia M., Martin, Nicholas G., Maerz, Winfried, McCarthy, Mark I., McKenzie, Colin A., Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D., Munroe, Patricia B., Njolstad, Inger, Pedersen, Nancy L., Power, Chris, Pramstaller, Peter P., Price, Jackie F., Psaty, Bruce M., Quertermous, Thomas, Rauramaa, Rainer, Saleheen, Danish, Salomaa, Veikko, Sanghera, Dharambir K., Saramies, Jouko, Schwarz, Peter E. H., Sheu, Wayne H-H, Shuldiner, Alan R., Siegbahn, Agneta, Spector, Tim D., Stefansson, Kari, Strachan, David P., Tayo, Bamidele O., Tremoli, Elena, Tuomilehto, Jaakko, Uusitupa, Matti, van Duijn, Cornelia M., Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J., Whitfield, John B., Wolffenbuttel, Bruce H. R., Ordovas, Jose M., Boerwinkle, Eric, Palmer, Colin N. A., Thorsteinsdottir, Unnur, Chasman, Daniel I., Rotter, Jerome I., Franks, Paul W., Ripatti, Samuli, Cupples, L. Adrienne, Sandhu, Manjinder S., Rich, Stephen S., Boehnke, Michael, Deloukas, Panos, Kathiresan, Sekar, Mohlke, Karen L., Ingelsson, Erik, Abecasis, Goncalo R., Willer, Cristen J., Schmidt, Ellen M., Sengupta, Sebanti, Peloso, Gina M., Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L., Mora, Samia, Beckmann, Jacques S., Bragg-Gresham, Jennifer L., Chang, Hsing-Yi, Demirkan, Ayse, Den Hertog, Heleen M., Do, Ron, Donnelly, Louise A., Ehret, Georg B., Esko, Tonu, Feitosa, Mary F., Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Fraser, Ross M., Freitag, Daniel F., Gurdasani, Deepti, Heikkila, Kauko, Hyppoenen, Elina, Isaacs, Aaron, Jackson, Anne U., Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E., Li, Xiaohui, Luan, Jian'an, Lyytikainen, Leo-Pekka, Magnusson, Patrik K. E., Mangino, Massimo, Mihailov, Evelin, Montasser, May E., Mueller-Nurasyid, Martina, Nolte, Ilja M., O'Connell, Jeffrey R., Palmer, Cameron D., Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K., Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J., Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M., Thorleifsson, Gudmar, Van den Herik, Evita G., Voight, Benjamin F., Volcik, Kelly A., Waite, Lindsay L., Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Ines, Been, Latonya F., Bolton, Jennifer L., Bonnycastle, Lori L., Brambilla, Paolo, Burnett, Mary S., Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S. F., Doering, Angela, Elliott, Paul, Epstein, Stephen E., Eyjolfsson, Gudmundur Ingi, Gigante, Bruna, Goodarzi, Mark O., Grallert, Harald, Gravito, Martha L., Groves, Christopher J., Hallmans, Goran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A., Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R., Kaleebu, Pontiano, Kastelein, John J. P., Khaw, Kay-Tee, Kim, Eric, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J. F., Mach, Francois, McArdle, Wendy L., Meisinger, Christa, Mitchell, Braxton D., Mueller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V. M., Nsubuga, Rebecca N., Olafsson, Isleifur, Ong, Ken K., Palotie, Aarno, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J., Reilly, Muredach P., Ridker, Paul M., Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stancakova, Alena, Stirrups, Kathleen, Swift, Amy J., Tiret, Laurence, Uitterlinden, Andre G., van Pelt, L. Joost, Vedantam, Sailaja, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F., Young, Elizabeth H., Zhao, Jing Hua, Adair, Linda S., Arveiler, Dominique, Assimes, Themistocles L., Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O., Boomsma, Dorret I., Borecki, Ingrid B., Bornstein, Stefan R., Bovet, Pascal, Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C., Chen, Yii-Der Ida, Collins, Francis S., Cooper, Richard S., Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B., Ferrieres, Jean, Ferrucci, Luigi, Freimer, Nelson B., Gieger, Christian, Groop, Leif C., Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Hingorani, Aroon, Hirschhorn, Joel N., Hofman, Albert, Hovingh, G. Kees, Hsiung, Chao Agnes, Humphries, Steve E., Hunt, Steven C., Hveem, Kristian, Iribarren, Carlos, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kaprio, Jaakko, Kesaniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S., Koudstaal, Peter J., Krauss, Ronald M., Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O., Laakso, Markku, Lakka, Timo A., Lind, Lars, Lindgren, Cecilia M., Martin, Nicholas G., Maerz, Winfried, McCarthy, Mark I., McKenzie, Colin A., Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D., Munroe, Patricia B., Njolstad, Inger, Pedersen, Nancy L., Power, Chris, Pramstaller, Peter P., Price, Jackie F., Psaty, Bruce M., Quertermous, Thomas, Rauramaa, Rainer, Saleheen, Danish, Salomaa, Veikko, Sanghera, Dharambir K., Saramies, Jouko, Schwarz, Peter E. H., Sheu, Wayne H-H, Shuldiner, Alan R., Siegbahn, Agneta, Spector, Tim D., Stefansson, Kari, Strachan, David P., Tayo, Bamidele O., Tremoli, Elena, Tuomilehto, Jaakko, Uusitupa, Matti, van Duijn, Cornelia M., Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J., Whitfield, John B., Wolffenbuttel, Bruce H. R., Ordovas, Jose M., Boerwinkle, Eric, Palmer, Colin N. A., Thorsteinsdottir, Unnur, Chasman, Daniel I., Rotter, Jerome I., Franks, Paul W., Ripatti, Samuli, Cupples, L. Adrienne, Sandhu, Manjinder S., Rich, Stephen S., Boehnke, Michael, Deloukas, Panos, Kathiresan, Sekar, Mohlke, Karen L., Ingelsson, Erik, and Abecasis, Goncalo R.
Abstract: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research., De sex sista författarna delar sistaförfattarskapet.
Published: 2013
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18. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

Author: Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, Prokopenko, Inga, Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, and Prokopenko, Inga
Abstract: Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimat, De fyra sista författarna delar sistaförfattarskapet.
Published: 2013
Full Text: View/download PDF

19. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

Author: Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., Hyppoenen, Elina, Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., and Hyppoenen, Elina
Abstract: Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH) D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH) D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH) D (p = 6.52x10(-27)). The BMI allele score was associated both with BMI (p = 6.30x10(-62)) and 25(OH) D (20.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH) D (p <= 8.07x10(-57) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH) D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH) D with BMI, a finding that was confirmed using data from the GIANT consortium (p >= 0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH) D, while any effects of lower 25(OH) D increasing BMI are likely to be small. Populati
Published: 2013
Full Text: View/download PDF

20. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

Author: Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., Hyppoenen, Elina, Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., and Hyppoenen, Elina
Abstract: Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH) D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH) D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH) D (p = 6.52x10(-27)). The BMI allele score was associated both with BMI (p = 6.30x10(-62)) and 25(OH) D (20.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH) D (p <= 8.07x10(-57) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH) D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH) D with BMI, a finding that was confirmed using data from the GIANT consortium (p >= 0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH) D, while any effects of lower 25(OH) D increasing BMI are likely to be small. Populati
Published: 2013
Full Text: View/download PDF

21. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

Author: Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, Prokopenko, Inga, Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, and Prokopenko, Inga
Abstract: Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimat, De fyra sista författarna delar sistaförfattarskapet.
Published: 2013
Full Text: View/download PDF

22. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

Author: Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, Prokopenko, Inga, Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, and Prokopenko, Inga
Abstract: Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimat, De fyra sista författarna delar sistaförfattarskapet.
Published: 2013
Full Text: View/download PDF

23. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

Author: Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., Hyppoenen, Elina, Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., and Hyppoenen, Elina
Abstract: Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH) D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH) D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH) D (p = 6.52x10(-27)). The BMI allele score was associated both with BMI (p = 6.30x10(-62)) and 25(OH) D (20.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH) D (p <= 8.07x10(-57) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH) D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH) D with BMI, a finding that was confirmed using data from the GIANT consortium (p >= 0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH) D, while any effects of lower 25(OH) D increasing BMI are likely to be small. Populati
Published: 2013
Full Text: View/download PDF

24. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

Author: Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, Prokopenko, Inga, Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, and Prokopenko, Inga
Abstract: Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimat, De fyra sista författarna delar sistaförfattarskapet.
Published: 2013
Full Text: View/download PDF

25. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

Author: Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., Hyppoenen, Elina, Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T., Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimaki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, Maerz, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas J., Jaervelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., and Hyppoenen, Elina
Abstract: Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH) D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH) D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH) D (p = 6.52x10(-27)). The BMI allele score was associated both with BMI (p = 6.30x10(-62)) and 25(OH) D (20.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH) D (p <= 8.07x10(-57) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH) D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH) D with BMI, a finding that was confirmed using data from the GIANT consortium (p >= 0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH) D, while any effects of lower 25(OH) D increasing BMI are likely to be small. Populati
Published: 2013
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26. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

Author: Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, Prokopenko, Inga, Fall, Tove, Hägg, Sara, Maegi, Reedik, Ploner, Alexander, Fischer, Krista, Horikoshi, Momoko, Sarin, Antti-Pekka, Thorleifsson, Gudmar, Ladenvall, Claes, Kals, Mart, Kuningas, Maris, Draisma, Harmen H. M., Ried, Janina S., van Zuydam, Natalie R., Huikari, Ville, Mangino, Massimo, Sonestedt, Emily, Benyamin, Beben, Nelson, Christopher P., Rivera, Natalia V., Kristiansson, Kati, Shen, Huei-yi, Havulinna, Aki S., Dehghan, Abbas, Donnelly, Louise A., Kaakinen, Marika, Nuotio, Marja-Liisa, Robertson, Neil, de Bruijn, Renee F. A. G., Ikram, M. Arfan, Amin, Najaf, Balmforth, Anthony J., Braund, Peter S., Doney, Alexander S. F., Doering, Angela, Elliott, Paul, Esko, Tonu, Franco, Oscar H., Gretarsdottir, Solveig, Hartikainen, Anna-Liisa, Heikkila, Kauko, Herzig, Karl-Heinz, Holm, Hilma, Hottenga, Jouke Jan, Hypponen, Elina, Illig, Thomas, Isaacs, Aaron, Isomaa, Bo, Karssen, Lennart C., Kettunen, Johannes, Koenig, Wolfgang, Kuulasmaa, Kari, Laatikainen, Tiina, Laitinen, Jaana, Lindgren, Cecilia, Lyssenko, Valeriya, Laara, Esa, Rayner, Nigel W., Mannisto, Satu, Pouta, Anneli, Rathmann, Wolfgang, Rivadeneira, Fernando, Ruokonen, Aimo, Savolainen, Markku J., Sijbrands, Eric J. G., Small, Kerrin S., Smit, Jan H., Steinthorsdottir, Valgerdur, Syvänen, Ann-Christine, Taanila, Anja, Tobin, Martin D., Uitterlinden, Andre G., Willems, Sara M., Willemsen, Gonneke, Witteman, Jacqueline, Perola, Markus, Evans, Alun, Ferrieres, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Ferrario, Marco M., Brambilla, Paolo, Hall, Alistair S., Heath, AndrewC., Madden, Pamela A. F., Martin, Nicholas G., Montgomery, Grant W., Whitfield, John B., Jula, Antti, Knekt, Paul, Oostra, Ben, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Smith, George Davey, Kaprio, Jaakko, Samani, Nilesh J., Gieger, Christian, Peters, Annette, Wichmann, H. -Erich, Boomsma, Dorret I., de Geus, Eco J. C., Tuomi, TiinaMaija, Power, Chris, Hammond, Christopher J., Spector, Tim D., Lind, Lars, Orho-Melander, Marju, Palmer, Colin Neil Alexander, Morris, Andrew D., Groop, Leif, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Vartiainen, Erkki, Hofman, Albert, Ripatti, Samuli, Metspalu, Andres, Thorsteinsdottir, Unnur, Stefansson, Kari, Pedersen, Nancy L., McCarthy, Mark I., Ingelsson, Erik, and Prokopenko, Inga
Abstract: Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimat, De fyra sista författarna delar sistaförfattarskapet.
Published: 2013
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26 results on '"Kaakinen, Marika A."'

1. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

2. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

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

4. Adiposity as a cause of cardiovascular disease : a Mendelian randomization study

5. Age- and sex-specific causal effects of adiposity on cardiovascular risk factors

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

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

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

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

10. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

11. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

12. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

13. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

14. Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

15. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

16. Common variants associated with plasma triglycerides and risk for coronary artery disease

17. Discovery and refinement of loci associated with lipid levels

18. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

19. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

20. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

21. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

22. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

23. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

24. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

25. Causal Relationship between Obesity and Vitamin D Status : Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

26. The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis

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26 results on '"Kaakinen, Marika A."'

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