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1. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author: Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel
Abstract: Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
Published: 2022
Full Text: View/download PDF

2. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author: Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel
Abstract: Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
Published: 2022
Full Text: View/download PDF

3. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author: Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel
Abstract: Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
Published: 2022
Full Text: View/download PDF

4. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author: Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel
Abstract: Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
Published: 2022
Full Text: View/download PDF

5. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author: Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel
Abstract: Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
Published: 2022
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6. Meta-analysis of exome array data identifies six novel genetic loci for lung function.

Author: Jackson, Victoria E, Latourelle, Jeanne C, Wain, Louise V, Smith, Albert V, Grove, Megan L, Bartz, Traci M, Obeidat, Ma'en, Province, Michael A, Gao, Wei, Qaiser, Beenish, Porteous, David J, Cassano, Patricia A, Ahluwalia, Tarunveer S, Grarup, Niels, Li, Jin, Altmaier, Elisabeth, Marten, Jonathan, Harris, Sarah E, Manichaikul, Ani, Pottinger, Tess D, Li-Gao, Ruifang, Lind-Thomsen, Allan, Mahajan, Anubha, Lahousse, Lies, Imboden, Medea, Teumer, Alexander, Prins, Bram, Lyytikäinen, Leo-Pekka, Eiriksdottir, Gudny, Franceschini, Nora, Sitlani, Colleen M, Brody, Jennifer A, Bossé, Yohan, Timens, Wim, Kraja, Aldi, Loukola, Anu, Tang, Wenbo, Liu, Yongmei, Bork-Jensen, Jette, Justesen, Johanne M, Linneberg, Allan, Lange, Leslie A, Rawal, Rajesh, Karrasch, Stefan, Huffman, Jennifer E, Smith, Blair H, Davies, Gail, Burkart, Kristin M, Mychaleckyj, Josyf C, Bonten, Tobias N, Enroth, Stefan, Lind, Lars, Brusselle, Guy G, Kumar, Ashish, Stubbe, Beate, Kähönen, Mika, Wyss, Annah B, Psaty, Bruce M, Heckbert, Susan R, Hao, Ke, Rantanen, Taina, Kritchevsky, Stephen B, Lohman, Kurt, Skaaby, Tea, Pisinger, Charlotta, Hansen, Torben, Schulz, Holger, Polasek, Ozren, Campbell, Archie, Starr, John M, Rich, Stephen S, Mook-Kanamori, Dennis O, Johansson, Åsa, Ingelsson, Erik, Uitterlinden, André G, Weiss, Stefan, Raitakari, Olli T, Gudnason, Vilmundur, North, Kari E, Gharib, Sina A, Sin, Don D, Taylor, Kent D, O'Connor, George T, Kaprio, Jaakko, Harris, Tamara B, Pederson, Oluf, Vestergaard, Henrik, Wilson, James G, Strauch, Konstantin, Hayward, Caroline, Kerr, Shona, Deary, Ian J, Barr, R Graham, de Mutsert, Renée, Gyllensten, Ulf, Morris, Andrew P, Ikram, M Arfan, Probst-Hensch, Nicole, Gläser, Sven, Zeggini, Eleftheria, Lehtimäki, Terho, Strachan, David P, Dupuis, Josée, Morrison, Alanna C, Hall, Ian P, Tobin, Martin D, London, Stephanie J, Jackson, Victoria E, Latourelle, Jeanne C, Wain, Louise V, Smith, Albert V, Grove, Megan L, Bartz, Traci M, Obeidat, Ma'en, Province, Michael A, Gao, Wei, Qaiser, Beenish, Porteous, David J, Cassano, Patricia A, Ahluwalia, Tarunveer S, Grarup, Niels, Li, Jin, Altmaier, Elisabeth, Marten, Jonathan, Harris, Sarah E, Manichaikul, Ani, Pottinger, Tess D, Li-Gao, Ruifang, Lind-Thomsen, Allan, Mahajan, Anubha, Lahousse, Lies, Imboden, Medea, Teumer, Alexander, Prins, Bram, Lyytikäinen, Leo-Pekka, Eiriksdottir, Gudny, Franceschini, Nora, Sitlani, Colleen M, Brody, Jennifer A, Bossé, Yohan, Timens, Wim, Kraja, Aldi, Loukola, Anu, Tang, Wenbo, Liu, Yongmei, Bork-Jensen, Jette, Justesen, Johanne M, Linneberg, Allan, Lange, Leslie A, Rawal, Rajesh, Karrasch, Stefan, Huffman, Jennifer E, Smith, Blair H, Davies, Gail, Burkart, Kristin M, Mychaleckyj, Josyf C, Bonten, Tobias N, Enroth, Stefan, Lind, Lars, Brusselle, Guy G, Kumar, Ashish, Stubbe, Beate, Kähönen, Mika, Wyss, Annah B, Psaty, Bruce M, Heckbert, Susan R, Hao, Ke, Rantanen, Taina, Kritchevsky, Stephen B, Lohman, Kurt, Skaaby, Tea, Pisinger, Charlotta, Hansen, Torben, Schulz, Holger, Polasek, Ozren, Campbell, Archie, Starr, John M, Rich, Stephen S, Mook-Kanamori, Dennis O, Johansson, Åsa, Ingelsson, Erik, Uitterlinden, André G, Weiss, Stefan, Raitakari, Olli T, Gudnason, Vilmundur, North, Kari E, Gharib, Sina A, Sin, Don D, Taylor, Kent D, O'Connor, George T, Kaprio, Jaakko, Harris, Tamara B, Pederson, Oluf, Vestergaard, Henrik, Wilson, James G, Strauch, Konstantin, Hayward, Caroline, Kerr, Shona, Deary, Ian J, Barr, R Graham, de Mutsert, Renée, Gyllensten, Ulf, Morris, Andrew P, Ikram, M Arfan, Probst-Hensch, Nicole, Gläser, Sven, Zeggini, Eleftheria, Lehtimäki, Terho, Strachan, David P, Dupuis, Josée, Morrison, Alanna C, Hall, Ian P, Tobin, Martin D, and London, Stephanie J
Abstract: Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
Published: 2018
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7. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Author: Ligthart, Symen, Vaez, Ahmad, Võsa, Urmo, Stathopoulou, Maria G, de Vries, Paul S, Prins, Bram P, Van der Most, Peter J, Tanaka, Toshiko, Naderi, Elnaz, Rose, Lynda M, Wu, Ying, Karlsson, Robert, Barbalic, Maja, Lin, Honghuang, Pool, René, Zhu, Gu, Macé, Aurélien, Sidore, Carlo, Trompet, Stella, Mangino, Massimo, Sabater-Lleal, Maria, Kemp, John P, Abbasi, Ali, Kacprowski, Tim, Verweij, Niek, Smith, Albert V, Huang, Tao, Marzi, Carola, Feitosa, Mary F, Lohman, Kurt K, Kleber, Marcus E, Milaneschi, Yuri, Mueller, Christian, Huq, Mahmudul, Vlachopoulou, Efthymia, Lyytikäinen, Leo-Pekka, Oldmeadow, Christopher, Deelen, Joris, Perola, Markus, Zhao, Jing Hua, Feenstra, Bjarke, Amini, Marzyeh, Lahti, Jari, Schraut, Katharina E, Fornage, Myriam, Suktitipat, Bhoom, Chen, Wei-Min, Li, Xiaohui, Nutile, Teresa, Malerba, Giovanni, Luan, Jian'an, Bak, Tom, Schork, Nicholas, Del Greco M, Fabiola, Thiering, Elisabeth, Mahajan, Anubha, Marioni, Riccardo E, Mihailov, Evelin, Eriksson, Joel, Ozel, Ayse Bilge, Zhang, Weihua, Nethander, Maria, Cheng, Yu-Ching, Aslibekyan, Stella, Ang, Wei, Gandin, Ilaria, Yengo, Loïc, Portas, Laura, Kooperberg, Charles, Hofer, Edith, Rajan, Kumar B, Schurmann, Claudia, den Hollander, Wouter, Ahluwalia, Tarunveer S, Zhao, Jing, Draisma, Harmen H M, Ford, Ian, Timpson, Nicholas, Teumer, Alexander, Huang, Hongyan, Wahl, Simone, Liu, YongMei, Huang, Jie, Uh, Hae-Won, Geller, Frank, Joshi, Peter K, Yanek, Lisa R, Trabetti, Elisabetta, Lehne, Benjamin, Vozzi, Diego, Verbanck, Marie, Biino, Ginevra, Saba, Yasaman, Meulenbelt, Ingrid, O'Connell, Jeff R, Laakso, Markku, Giulianini, Franco, Magnusson, Patrik K E, Ballantyne, Christie M, Hottenga, Jouke Jan, Montgomery, Grant W, Rivadineira, Fernando, Rueedi, Rico, Steri, Maristella, Herzig, Karl-Heinz, Stott, David J, Menni, Cristina, Frånberg, Mattias, St Pourcain, Beate, Felix, Stephan B, Pers, Tune H, Bakker, Stephan J L, Kraft, Peter, Peters, Annette, Vaidya, Dhananjay, Delgado, Graciela, Smit, Johannes H, Großmann, Vera, Sinisalo, Juha, Seppälä, Ilkka, Williams, Stephen R, Holliday, Elizabeth G, Moed, Matthijs, Langenberg, Claudia, Räikkönen, Katri, Ding, Jingzhong, Campbell, Harry, Sale, Michele M, Chen, Yii-Der I, James, Alan L, Ruggiero, Daniela, Soranzo, Nicole, Hartman, Catharina A, Smith, Erin N, Berenson, Gerald S, Fuchsberger, Christian, Hernandez, Dena, Tiesler, Carla M T, Giedraitis, Vilmantas, Liewald, David, Fischer, Krista, Mellström, Dan, Larsson, Anders, Wang, Yunmei, Scott, William R, Lorentzon, Matthias, Beilby, John, Ryan, Kathleen A, Pennell, Craig E, Vuckovic, Dragana, Balkau, Beverly, Concas, Maria Pina, Schmidt, Reinhold, Mendes de Leon, Carlos F, Bottinger, Erwin P, Kloppenburg, Margreet, Paternoster, Lavinia, Boehnke, Michael, Musk, A W, Willemsen, Gonneke, Evans, David M, Madden, Pamela A F, Kähönen, Mika, Kutalik, Zoltán, Zoledziewska, Magdalena, Karhunen, Ville, Kritchevsky, Stephen B, Sattar, Naveed, Lachance, Genevieve, Clarke, Robert, Harris, Tamara B, Raitakari, Olli T, Attia, John R, van Heemst, Diana, Kajantie, Eero, Sorice, Rossella, Gambaro, Giovanni, Scott, Robert A, Hicks, Andrew A, Ferrucci, Luigi, Standl, Marie, Lindgren, Cecilia M, Starr, John M, Karlsson, Magnus, Lind, Lars, Li, Jun Z, Chambers, John C, Mori, Trevor A, de Geus, Eco J C N, Heath, Andrew C, Martin, Nicholas G, Auvinen, Juha, Buckley, Brendan M, de Craen, Anton J M, Waldenberger, Melanie, Strauch, Konstantin, Meitinger, Thomas, Scott, Rodney J, McEvoy, Mark, Beekman, Marian, Bombieri, Cristina, Ridker, Paul M, Mohlke, Karen L, Pedersen, Nancy L, Morrison, Alanna C, Boomsma, Dorret I, Whitfield, John B, Strachan, David P, Hofman, Albert, Vollenweider, Peter, Cucca, Francesco, Jarvelin, Marjo-Riitta, Jukema, J Wouter, Spector, Tim D, Hamsten, Anders, Zeller, Tanja, Uitterlinden, André G, Nauck, Matthias, Gudnason, Vilmundur, Qi, Lu, Grallert, Harald, Borecki, Ingrid B, Rotter, Jerome I, März, Winfried, Wild, Philipp S, Lokki, Marja-Liisa, Boyle, Michael, Salomaa, Veikko, Melbye, Mads, Eriksson, Johan G, Wilson, James F, Penninx, Brenda W J H, Becker, Diane M, Worrall, Bradford B, Gibson, Greg, Krauss, Ronald M, Ciullo, Marina, Zaza, Gianluigi, Wareham, Nicholas J, Oldehinkel, Albertine J, Palmer, Lyle J, Murray, Sarah S, Pramstaller, Peter P, Bandinelli, Stefania, Heinrich, Joachim, Ingelsson, Erik, Deary, Ian J, Mägi, Reedik, Vandenput, Liesbeth, van der Harst, Pim, Desch, Karl C, Kooner, Jaspal S, Ohlsson, Claes, Hayward, Caroline, Lehtimäki, Terho, Shuldiner, Alan R, Arnett, Donna K, Beilin, Lawrence J, Robino, Antonietta, Froguel, Philippe, Pirastu, Mario, Jess, Tine, Koenig, Wolfgang, Loos, Ruth J F, Evans, Denis A, Schmidt, Helena, Smith, George Davey, Slagboom, P Eline, Eiriksdottir, Gudny, Morris, Andrew P, Psaty, Bruce M, Tracy, Russell P, Nolte, Ilja M, Boerwinkle, Eric, Visvikis-Siest, Sophie, Reiner, Alex P, Gross, Myron, Bis, Joshua C, Franke, Lude, Franco, Oscar H, Benjamin, Emelia J, Chasman, Daniel I, Dupuis, Josée, Snieder, Harold, Dehghan, Abbas, Alizadeh, Behrooz Z, Ligthart, Symen, Vaez, Ahmad, Võsa, Urmo, Stathopoulou, Maria G, de Vries, Paul S, Prins, Bram P, Van der Most, Peter J, Tanaka, Toshiko, Naderi, Elnaz, Rose, Lynda M, Wu, Ying, Karlsson, Robert, Barbalic, Maja, Lin, Honghuang, Pool, René, Zhu, Gu, Macé, Aurélien, Sidore, Carlo, Trompet, Stella, Mangino, Massimo, Sabater-Lleal, Maria, Kemp, John P, Abbasi, Ali, Kacprowski, Tim, Verweij, Niek, Smith, Albert V, Huang, Tao, Marzi, Carola, Feitosa, Mary F, Lohman, Kurt K, Kleber, Marcus E, Milaneschi, Yuri, Mueller, Christian, Huq, Mahmudul, Vlachopoulou, Efthymia, Lyytikäinen, Leo-Pekka, Oldmeadow, Christopher, Deelen, Joris, Perola, Markus, Zhao, Jing Hua, Feenstra, Bjarke, Amini, Marzyeh, Lahti, Jari, Schraut, Katharina E, Fornage, Myriam, Suktitipat, Bhoom, Chen, Wei-Min, Li, Xiaohui, Nutile, Teresa, Malerba, Giovanni, Luan, Jian'an, Bak, Tom, Schork, Nicholas, Del Greco M, Fabiola, Thiering, Elisabeth, Mahajan, Anubha, Marioni, Riccardo E, Mihailov, Evelin, Eriksson, Joel, Ozel, Ayse Bilge, Zhang, Weihua, Nethander, Maria, Cheng, Yu-Ching, Aslibekyan, Stella, Ang, Wei, Gandin, Ilaria, Yengo, Loïc, Portas, Laura, Kooperberg, Charles, Hofer, Edith, Rajan, Kumar B, Schurmann, Claudia, den Hollander, Wouter, Ahluwalia, Tarunveer S, Zhao, Jing, Draisma, Harmen H M, Ford, Ian, Timpson, Nicholas, Teumer, Alexander, Huang, Hongyan, Wahl, Simone, Liu, YongMei, Huang, Jie, Uh, Hae-Won, Geller, Frank, Joshi, Peter K, Yanek, Lisa R, Trabetti, Elisabetta, Lehne, Benjamin, Vozzi, Diego, Verbanck, Marie, Biino, Ginevra, Saba, Yasaman, Meulenbelt, Ingrid, O'Connell, Jeff R, Laakso, Markku, Giulianini, Franco, Magnusson, Patrik K E, Ballantyne, Christie M, Hottenga, Jouke Jan, Montgomery, Grant W, Rivadineira, Fernando, Rueedi, Rico, Steri, Maristella, Herzig, Karl-Heinz, Stott, David J, Menni, Cristina, Frånberg, Mattias, St Pourcain, Beate, Felix, Stephan B, Pers, Tune H, Bakker, Stephan J L, Kraft, Peter, Peters, Annette, Vaidya, Dhananjay, Delgado, Graciela, Smit, Johannes H, Großmann, Vera, Sinisalo, Juha, Seppälä, Ilkka, Williams, Stephen R, Holliday, Elizabeth G, Moed, Matthijs, Langenberg, Claudia, Räikkönen, Katri, Ding, Jingzhong, Campbell, Harry, Sale, Michele M, Chen, Yii-Der I, James, Alan L, Ruggiero, Daniela, Soranzo, Nicole, Hartman, Catharina A, Smith, Erin N, Berenson, Gerald S, Fuchsberger, Christian, Hernandez, Dena, Tiesler, Carla M T, Giedraitis, Vilmantas, Liewald, David, Fischer, Krista, Mellström, Dan, Larsson, Anders, Wang, Yunmei, Scott, William R, Lorentzon, Matthias, Beilby, John, Ryan, Kathleen A, Pennell, Craig E, Vuckovic, Dragana, Balkau, Beverly, Concas, Maria Pina, Schmidt, Reinhold, Mendes de Leon, Carlos F, Bottinger, Erwin P, Kloppenburg, Margreet, Paternoster, Lavinia, Boehnke, Michael, Musk, A W, Willemsen, Gonneke, Evans, David M, Madden, Pamela A F, Kähönen, Mika, Kutalik, Zoltán, Zoledziewska, Magdalena, Karhunen, Ville, Kritchevsky, Stephen B, Sattar, Naveed, Lachance, Genevieve, Clarke, Robert, Harris, Tamara B, Raitakari, Olli T, Attia, John R, van Heemst, Diana, Kajantie, Eero, Sorice, Rossella, Gambaro, Giovanni, Scott, Robert A, Hicks, Andrew A, Ferrucci, Luigi, Standl, Marie, Lindgren, Cecilia M, Starr, John M, Karlsson, Magnus, Lind, Lars, Li, Jun Z, Chambers, John C, Mori, Trevor A, de Geus, Eco J C N, Heath, Andrew C, Martin, Nicholas G, Auvinen, Juha, Buckley, Brendan M, de Craen, Anton J M, Waldenberger, Melanie, Strauch, Konstantin, Meitinger, Thomas, Scott, Rodney J, McEvoy, Mark, Beekman, Marian, Bombieri, Cristina, Ridker, Paul M, Mohlke, Karen L, Pedersen, Nancy L, Morrison, Alanna C, Boomsma, Dorret I, Whitfield, John B, Strachan, David P, Hofman, Albert, Vollenweider, Peter, Cucca, Francesco, Jarvelin, Marjo-Riitta, Jukema, J Wouter, Spector, Tim D, Hamsten, Anders, Zeller, Tanja, Uitterlinden, André G, Nauck, Matthias, Gudnason, Vilmundur, Qi, Lu, Grallert, Harald, Borecki, Ingrid B, Rotter, Jerome I, März, Winfried, Wild, Philipp S, Lokki, Marja-Liisa, Boyle, Michael, Salomaa, Veikko, Melbye, Mads, Eriksson, Johan G, Wilson, James F, Penninx, Brenda W J H, Becker, Diane M, Worrall, Bradford B, Gibson, Greg, Krauss, Ronald M, Ciullo, Marina, Zaza, Gianluigi, Wareham, Nicholas J, Oldehinkel, Albertine J, Palmer, Lyle J, Murray, Sarah S, Pramstaller, Peter P, Bandinelli, Stefania, Heinrich, Joachim, Ingelsson, Erik, Deary, Ian J, Mägi, Reedik, Vandenput, Liesbeth, van der Harst, Pim, Desch, Karl C, Kooner, Jaspal S, Ohlsson, Claes, Hayward, Caroline, Lehtimäki, Terho, Shuldiner, Alan R, Arnett, Donna K, Beilin, Lawrence J, Robino, Antonietta, Froguel, Philippe, Pirastu, Mario, Jess, Tine, Koenig, Wolfgang, Loos, Ruth J F, Evans, Denis A, Schmidt, Helena, Smith, George Davey, Slagboom, P Eline, Eiriksdottir, Gudny, Morris, Andrew P, Psaty, Bruce M, Tracy, Russell P, Nolte, Ilja M, Boerwinkle, Eric, Visvikis-Siest, Sophie, Reiner, Alex P, Gross, Myron, Bis, Joshua C, Franke, Lude, Franco, Oscar H, Benjamin, Emelia J, Chasman, Daniel I, Dupuis, Josée, Snieder, Harold, Dehghan, Abbas, and Alizadeh, Behrooz Z
Abstract: C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.
Published: 2018
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8. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

Author: Evangelou, Evangelos, Warren, Helen R, Mosen-Ansorena, David, Mifsud, Borbala, Pazoki, Raha, Gao, He, Ntritsos, Georgios, Dimou, Niki, Cabrera, Claudia P, Karaman, Ibrahim, Ng, Fu Liang, Evangelou, Marina, Witkowska, Katarzyna, Tzanis, Evan, Hellwege, Jacklyn N, Giri, Ayush, Velez Edwards, Digna R, Sun, Yan V, Cho, Kelly, Gaziano, J Michael, Wilson, Peter W F, Tsao, Philip S, Kovesdy, Csaba P, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Debette, Stéphanie, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian'an, Mangino, Massimo, Oldmeadow, Christopher, Prins, Bram Peter, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Amouyel, Philippe, Connell, John, de Mutsert, Renée, Doney, Alex S F, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Demirkale, Cumhur Yusuf, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Erzurumluoglu, A Mesut, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf B., Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Jukema, J Wouter, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C M, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth J F, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O'Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, Penninx, Brenda W J H, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Nguyen, Quang Tri, Raitakari, Olli T, Ren, Meixia, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Vergnaud, Anne-Claire, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna M M, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin N A, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Hung, Adriana M, O'Donnell, Christopher J, Edwards, Todd L, Psaty, Bruce M, Tzoulaki, Ioanna, Barnes, Michael R, Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Evangelou, Evangelos, Warren, Helen R, Mosen-Ansorena, David, Mifsud, Borbala, Pazoki, Raha, Gao, He, Ntritsos, Georgios, Dimou, Niki, Cabrera, Claudia P, Karaman, Ibrahim, Ng, Fu Liang, Evangelou, Marina, Witkowska, Katarzyna, Tzanis, Evan, Hellwege, Jacklyn N, Giri, Ayush, Velez Edwards, Digna R, Sun, Yan V, Cho, Kelly, Gaziano, J Michael, Wilson, Peter W F, Tsao, Philip S, Kovesdy, Csaba P, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Debette, Stéphanie, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian'an, Mangino, Massimo, Oldmeadow, Christopher, Prins, Bram Peter, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Amouyel, Philippe, Connell, John, de Mutsert, Renée, Doney, Alex S F, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Demirkale, Cumhur Yusuf, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Erzurumluoglu, A Mesut, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf B., Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Jukema, J Wouter, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C M, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth J F, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O'Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, Penninx, Brenda W J H, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Nguyen, Quang Tri, Raitakari, Olli T, Ren, Meixia, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Vergnaud, Anne-Claire, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna M M, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin N A, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Hung, Adriana M, O'Donnell, Christopher J, Edwards, Todd L, Psaty, Bruce M, Tzoulaki, Ioanna, Barnes, Michael R, Wain, Louise V, Elliott, Paul, and Caulfield, Mark J
Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
Published: 2018
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9. Genome-wide physical activity interactions in adiposity : A meta-analysis of 200,452 adults.

Author: Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, Kilpeläinen, Tuomas O, Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, and Kilpeläinen, Tuomas O
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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10. Genome-wide physical activity interactions in adiposity : A meta-analysis of 200,452 adults.

Author: Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, Kilpeläinen, Tuomas O, Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, and Kilpeläinen, Tuomas O
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
Full Text: View/download PDF

11. Genome-wide physical activity interactions in adiposity : A meta-analysis of 200,452 adults.

Author: Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, Kilpeläinen, Tuomas O, Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, and Kilpeläinen, Tuomas O
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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12. Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

Author: Aschard, Hugues, Tobin, Martin D, Hancock, Dana B, Skurnik, David, Sood, Akshay, James, Alan, Vernon Smith, Albert, Manichaikul, Ani W, Campbell, Archie, Prins, Bram P, Hayward, Caroline, Loth, Daan W, Porteous, David J, Strachan, David P, Zeggini, Eleftheria, O'Connor, George T, Brusselle, Guy G, Boezen, H Marike, Schulz, Holger, Deary, Ian J, Hall, Ian P, Rudan, Igor, Kaprio, Jaakko, Wilson, James F, Wilk, Jemma B, Huffman, Jennifer E, Hua Zhao, Jing, de Jong, Kim, Lyytikäinen, Leo-Pekka, Wain, Louise V, Jarvelin, Marjo-Riitta, Kähönen, Mika, Fornage, Myriam, Polasek, Ozren, Cassano, Patricia A, Barr, R Graham, Rawal, Rajesh, Harris, Sarah E, Gharib, Sina A, Enroth, Stefan, Heckbert, Susan R, Lehtimäki, Terho, Gyllensten, Ulf B., Society Scientific Group, Understanding, Jackson, Victoria E, Gudnason, Vilmundur, Tang, Wenbo, Dupuis, Josée, Soler Artigas, María, Joshi, Amit D, London, Stephanie J, Kraft, Peter, Aschard, Hugues, Tobin, Martin D, Hancock, Dana B, Skurnik, David, Sood, Akshay, James, Alan, Vernon Smith, Albert, Manichaikul, Ani W, Campbell, Archie, Prins, Bram P, Hayward, Caroline, Loth, Daan W, Porteous, David J, Strachan, David P, Zeggini, Eleftheria, O'Connor, George T, Brusselle, Guy G, Boezen, H Marike, Schulz, Holger, Deary, Ian J, Hall, Ian P, Rudan, Igor, Kaprio, Jaakko, Wilson, James F, Wilk, Jemma B, Huffman, Jennifer E, Hua Zhao, Jing, de Jong, Kim, Lyytikäinen, Leo-Pekka, Wain, Louise V, Jarvelin, Marjo-Riitta, Kähönen, Mika, Fornage, Myriam, Polasek, Ozren, Cassano, Patricia A, Barr, R Graham, Rawal, Rajesh, Harris, Sarah E, Gharib, Sina A, Enroth, Stefan, Heckbert, Susan R, Lehtimäki, Terho, Gyllensten, Ulf B., Society Scientific Group, Understanding, Jackson, Victoria E, Gudnason, Vilmundur, Tang, Wenbo, Dupuis, Josée, Soler Artigas, María, Joshi, Amit D, London, Stephanie J, and Kraft, Peter
Abstract: BACKGROUND: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. METHODS: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. RESULTS: We identified an interaction (βint = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV 1: /FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. CONCLUSIONS: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
Published: 2017
Full Text: View/download PDF

13. Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

Author: Aschard, Hugues, Tobin, Martin D, Hancock, Dana B, Skurnik, David, Sood, Akshay, James, Alan, Vernon Smith, Albert, Manichaikul, Ani W, Campbell, Archie, Prins, Bram P, Hayward, Caroline, Loth, Daan W, Porteous, David J, Strachan, David P, Zeggini, Eleftheria, O'Connor, George T, Brusselle, Guy G, Boezen, H Marike, Schulz, Holger, Deary, Ian J, Hall, Ian P, Rudan, Igor, Kaprio, Jaakko, Wilson, James F, Wilk, Jemma B, Huffman, Jennifer E, Hua Zhao, Jing, de Jong, Kim, Lyytikäinen, Leo-Pekka, Wain, Louise V, Jarvelin, Marjo-Riitta, Kähönen, Mika, Fornage, Myriam, Polasek, Ozren, Cassano, Patricia A, Barr, R Graham, Rawal, Rajesh, Harris, Sarah E, Gharib, Sina A, Enroth, Stefan, Heckbert, Susan R, Lehtimäki, Terho, Gyllensten, Ulf B., Society Scientific Group, Understanding, Jackson, Victoria E, Gudnason, Vilmundur, Tang, Wenbo, Dupuis, Josée, Soler Artigas, María, Joshi, Amit D, London, Stephanie J, Kraft, Peter, Aschard, Hugues, Tobin, Martin D, Hancock, Dana B, Skurnik, David, Sood, Akshay, James, Alan, Vernon Smith, Albert, Manichaikul, Ani W, Campbell, Archie, Prins, Bram P, Hayward, Caroline, Loth, Daan W, Porteous, David J, Strachan, David P, Zeggini, Eleftheria, O'Connor, George T, Brusselle, Guy G, Boezen, H Marike, Schulz, Holger, Deary, Ian J, Hall, Ian P, Rudan, Igor, Kaprio, Jaakko, Wilson, James F, Wilk, Jemma B, Huffman, Jennifer E, Hua Zhao, Jing, de Jong, Kim, Lyytikäinen, Leo-Pekka, Wain, Louise V, Jarvelin, Marjo-Riitta, Kähönen, Mika, Fornage, Myriam, Polasek, Ozren, Cassano, Patricia A, Barr, R Graham, Rawal, Rajesh, Harris, Sarah E, Gharib, Sina A, Enroth, Stefan, Heckbert, Susan R, Lehtimäki, Terho, Gyllensten, Ulf B., Society Scientific Group, Understanding, Jackson, Victoria E, Gudnason, Vilmundur, Tang, Wenbo, Dupuis, Josée, Soler Artigas, María, Joshi, Amit D, London, Stephanie J, and Kraft, Peter
Abstract: BACKGROUND: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. METHODS: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. RESULTS: We identified an interaction (βint = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV 1: /FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. CONCLUSIONS: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
Published: 2017
Full Text: View/download PDF

14. Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

Author: Aschard, Hugues, Tobin, Martin D, Hancock, Dana B, Skurnik, David, Sood, Akshay, James, Alan, Vernon Smith, Albert, Manichaikul, Ani W, Campbell, Archie, Prins, Bram P, Hayward, Caroline, Loth, Daan W, Porteous, David J, Strachan, David P, Zeggini, Eleftheria, O'Connor, George T, Brusselle, Guy G, Boezen, H Marike, Schulz, Holger, Deary, Ian J, Hall, Ian P, Rudan, Igor, Kaprio, Jaakko, Wilson, James F, Wilk, Jemma B, Huffman, Jennifer E, Hua Zhao, Jing, de Jong, Kim, Lyytikäinen, Leo-Pekka, Wain, Louise V, Jarvelin, Marjo-Riitta, Kähönen, Mika, Fornage, Myriam, Polasek, Ozren, Cassano, Patricia A, Barr, R Graham, Rawal, Rajesh, Harris, Sarah E, Gharib, Sina A, Enroth, Stefan, Heckbert, Susan R, Lehtimäki, Terho, Gyllensten, Ulf B., Society Scientific Group, Understanding, Jackson, Victoria E, Gudnason, Vilmundur, Tang, Wenbo, Dupuis, Josée, Soler Artigas, María, Joshi, Amit D, London, Stephanie J, Kraft, Peter, Aschard, Hugues, Tobin, Martin D, Hancock, Dana B, Skurnik, David, Sood, Akshay, James, Alan, Vernon Smith, Albert, Manichaikul, Ani W, Campbell, Archie, Prins, Bram P, Hayward, Caroline, Loth, Daan W, Porteous, David J, Strachan, David P, Zeggini, Eleftheria, O'Connor, George T, Brusselle, Guy G, Boezen, H Marike, Schulz, Holger, Deary, Ian J, Hall, Ian P, Rudan, Igor, Kaprio, Jaakko, Wilson, James F, Wilk, Jemma B, Huffman, Jennifer E, Hua Zhao, Jing, de Jong, Kim, Lyytikäinen, Leo-Pekka, Wain, Louise V, Jarvelin, Marjo-Riitta, Kähönen, Mika, Fornage, Myriam, Polasek, Ozren, Cassano, Patricia A, Barr, R Graham, Rawal, Rajesh, Harris, Sarah E, Gharib, Sina A, Enroth, Stefan, Heckbert, Susan R, Lehtimäki, Terho, Gyllensten, Ulf B., Society Scientific Group, Understanding, Jackson, Victoria E, Gudnason, Vilmundur, Tang, Wenbo, Dupuis, Josée, Soler Artigas, María, Joshi, Amit D, London, Stephanie J, and Kraft, Peter
Abstract: BACKGROUND: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. METHODS: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. RESULTS: We identified an interaction (βint = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV 1: /FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. CONCLUSIONS: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
Published: 2017
Full Text: View/download PDF

15. Genome-wide physical activity interactions in adiposity : A meta-analysis of 200,452 adults.

Author: Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, Kilpeläinen, Tuomas O, Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, and Kilpeläinen, Tuomas O
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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16. Genome-wide physical activity interactions in adiposity : A meta-analysis of 200,452 adults.

Author: Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, Kilpeläinen, Tuomas O, Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, and Kilpeläinen, Tuomas O
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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17. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, Fox, Caroline S, Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, and Fox, Caroline S
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways., Lars Lind ingår i ECHOGen Consortium
Published: 2016
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18. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author: Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, Loos, Ruth J F, Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, and Loos, Ruth J F
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Published: 2016
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19. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author: Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, Loos, Ruth J F, Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, and Loos, Ruth J F
Abstract: Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Published: 2016
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20. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, Fox, Caroline S, Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, and Fox, Caroline S
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways., Lars Lind ingår i ECHOGen Consortium
Published: 2016
Full Text: View/download PDF

21. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, Fox, Caroline S, Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, and Fox, Caroline S
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways., Lars Lind ingår i ECHOGen Consortium
Published: 2016
Full Text: View/download PDF

22. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author: Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, Loos, Ruth J F, Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, and Loos, Ruth J F
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Published: 2016
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23. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author: Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, Loos, Ruth J F, Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, and Loos, Ruth J F
Abstract: Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Published: 2016
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24. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author: Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, Loos, Ruth J F, Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, and Loos, Ruth J F
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Published: 2016
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25. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author: Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, Loos, Ruth J F, Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, and Loos, Ruth J F
Abstract: Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Published: 2016
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26. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, Fox, Caroline S, Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, and Fox, Caroline S
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways., Lars Lind ingår i ECHOGen Consortium
Published: 2016
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27. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author: Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, Loos, Ruth J F, Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, and Loos, Ruth J F
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Published: 2016
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28. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author: Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, Loos, Ruth J F, Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, and Loos, Ruth J F
Abstract: Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Published: 2016
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29. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, Fox, Caroline S, Pattaro, Cristian, Teumer, Alexander, Gorski, Mathias, Chu, Audrey Y, Li, Man, Mijatovic, Vladan, Garnaas, Maija, Tin, Adrienne, Sorice, Rossella, Li, Yong, Taliun, Daniel, Olden, Matthias, Foster, Meredith, Yang, Qiong, Chen, Ming-Huei, Pers, Tune H, Johnson, Andrew D, Ko, Yi-An, Fuchsberger, Christian, Tayo, Bamidele, Nalls, Michael, Feitosa, Mary F, Isaacs, Aaron, Dehghan, Abbas, d'Adamo, Pio, Adeyemo, Adebowale, Dieffenbach, Aida Karina, Zonderman, Alan B, Nolte, Ilja M, van der Most, Peter J, Wright, Alan F, Shuldiner, Alan R, Morrison, Alanna C, Hofman, Albert, Smith, Albert V, Dreisbach, Albert W, Franke, Andre, Uitterlinden, Andre G, Metspalu, Andres, Tonjes, Anke, Lupo, Antonio, Robino, Antonietta, Johansson, Åsa, Demirkan, Ayse, Kollerits, Barbara, Freedman, Barry I, Ponte, Belen, Oostra, Ben A, Paulweber, Bernhard, Krämer, Bernhard K, Mitchell, Braxton D, Buckley, Brendan M, Peralta, Carmen A, Hayward, Caroline, Helmer, Catherine, Rotimi, Charles N, Shaffer, Christian M, Müller, Christian, Sala, Cinzia, van Duijn, Cornelia M, Saint-Pierre, Aude, Ackermann, Daniel, Shriner, Daniel, Ruggiero, Daniela, Toniolo, Daniela, Lu, Yingchang, Cusi, Daniele, Czamara, Darina, Ellinghaus, David, Siscovick, David S, Ruderfer, Douglas, Gieger, Christian, Grallert, Harald, Rochtchina, Elena, Atkinson, Elizabeth J, Holliday, Elizabeth G, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Murgia, Federico, Rivadeneira, Fernando, Ernst, Florian, Kronenberg, Florian, Hu, Frank B, Navis, Gerjan J, Curhan, Gary C, Ehret, George B, Homuth, Georg, Coassin, Stefan, Thun, Gian-Andri, Pistis, Giorgio, Gambaro, Giovanni, Malerba, Giovanni, Montgomery, Grant W, Eiriksdottir, Gudny, Jacobs, Gunnar, Li, Guo, Wichmann, H-Erich, Campbell, Harry, Schmidt, Helena, Wallaschofski, Henri, Völzke, Henry, Brenner, Hermann, Kroemer, Heyo K, Kramer, Holly, Lin, Honghuang, Mateo Leach, I, Ford, Ian, Guessous, Idris, Rudan, Igor, Prokopenko, Inga, Borecki, Ingrid, Heid, Iris M, Kolcic, Ivana, Persico, Ivana, Jukema, J Wouter, Wilson, James F, Felix, Janine F, Divers, Jasmin, Lambert, Jean-Charles, Stafford, Jeanette M, Gaspoz, Jean-Michel, Smith, Jennifer A, Faul, Jessica D, Wang, Jie Jin, Ding, Jingzhong, Hirschhorn, Joel N, Attia, John, Whitfield, John B, Chalmers, John, Viikari, Jorma, Coresh, Josef, Denny, Joshua C, Karjalainen, Juha, Fernandes, Jyotika K, Endlich, Karlhans, Butterbach, Katja, Keene, Keith L, Lohman, Kurt, Portas, Laura, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Yengo, Loic, Franke, Lude, Ferrucci, Luigi, Rose, Lynda M, Kedenko, Lyudmyla, Rao, Madhumathi, Struchalin, Maksim, Kleber, Marcus E, Cavalieri, Margherita, Haun, Margot, Cornelis, Marilyn C, Ciullo, Marina, Pirastu, Mario, de Andrade, Mariza, McEvoy, Mark A, Woodward, Mark, Adam, Martin, Cocca, Massimiliano, Nauck, Matthias, Imboden, Medea, Waldenberger, Melanie, Pruijm, Menno, Metzger, Marie, Stumvoll, Michael, Evans, Michele K, Sale, Michele M, Kähönen, Mika, Boban, Mladen, Bochud, Murielle, Rheinberger, Myriam, Verweij, Niek, Bouatia-Naji, Nabila, Martin, Nicholas G, Hastie, Nick, Probst-Hensch, Nicole, Soranzo, Nicole, Devuyst, Olivier, Raitakari, Olli, Gottesman, Omri, Franco, Oscar H, Polasek, Ozren, Gasparini, Paolo, Munroe, Patricia B, Ridker, Paul M, Mitchell, Paul, Muntner, Paul, Meisinger, Christa, Smit, Johannes H, Kovacs, Peter, Wild, Philipp S, Froguel, Philippe, Rettig, Rainer, Mägi, Reedik, Biffar, Reiner, Schmidt, Reinhold, Middelberg, Rita P S, Carroll, Robert J, Penninx, Brenda W, Scott, Rodney J, Katz, Ronit, Sedaghat, Sanaz, Wild, Sarah H, Kardia, Sharon L R, Ulivi, Sheila, Hwang, Shih-Jen, Enroth, Stefan, Kloiber, Stefan, Trompet, Stella, Stengel, Benedicte, Hancock, Stephen J, Turner, Stephen T, Rosas, Sylvia E, Stracke, Sylvia, Harris, Tamara B, Zeller, Tanja, Zemunik, Tatijana, Lehtimäki, Terho, Illig, Thomas, Aspelund, Thor, Nikopensius, Tiit, Esko, Tonu, Tanaka, Toshiko, Gyllensten, Ulf, Völker, Uwe, Emilsson, Valur, Vitart, Veronique, Aalto, Ville, Gudnason, Vilmundur, Chouraki, Vincent, Chen, Wei-Min, Igl, Wilmar, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Loos, Ruth J F, Liu, Yongmei, Snieder, Harold, Pramstaller, Peter P, Parsa, Afshin, O'Connell, Jeffrey R, Susztak, Katalin, Hamet, Pavel, Tremblay, Johanne, de Boer, Ian H, Böger, Carsten A, Goessling, Wolfram, Chasman, Daniel I, Köttgen, Anna, Kao, W H Linda, and Fox, Caroline S
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways., Lars Lind ingår i ECHOGen Consortium
Published: 2016
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30. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author: Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, Loos, Ruth J F, Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, and Loos, Ruth J F
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Published: 2016
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31. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author: Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, Loos, Ruth J F, Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Greco M, Fabiola Del, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton J N, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, and Loos, Ruth J F
Abstract: Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Published: 2016
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32. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author: Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, Tobin, Martin D, Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, and Tobin, Martin D
Abstract: Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
Published: 2015
Full Text: View/download PDF

33. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author: Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, Tobin, Martin D, Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, and Tobin, Martin D
Abstract: Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
Published: 2015
Full Text: View/download PDF

34. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author: Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, Tobin, Martin D, Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, and Tobin, Martin D
Abstract: Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
Published: 2015
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35. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author: Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, Tobin, Martin D, Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, and Tobin, Martin D
Abstract: Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
Published: 2015
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36. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

Author: Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, Tobin, Martin D, Soler Artigas, María, Wain, Louise V, Miller, Suzanne, Kheirallah, Abdul Kader, Huffman, Jennifer E, Ntalla, Ioanna, Shrine, Nick, Obeidat, Ma'en, Trochet, Holly, McArdle, Wendy L, Alves, Alexessander Couto, Hui, Jennie, Zhao, Jing Hua, Joshi, Peter K, Teumer, Alexander, Albrecht, Eva, Imboden, Medea, Rawal, Rajesh, Lopez, Lorna M, Marten, Jonathan, Enroth, Stefan, Surakka, Ida, Polasek, Ozren, Lyytikäinen, Leo-Pekka, Granell, Raquel, Hysi, Pirro G, Flexeder, Claudia, Mahajan, Anubha, Beilby, John, Bossé, Yohan, Brandsma, Corry-Anke, Campbell, Harry, Gieger, Christian, Gläser, Sven, González, Juan R, Grallert, Harald, Hammond, Chris J, Harris, Sarah E, Hartikainen, Anna-Liisa, Heliövaara, Markku, Henderson, John, Hocking, Lynne, Horikoshi, Momoko, Hutri-Kähönen, Nina, Ingelsson, Erik, Johansson, Åsa, Kemp, John P, Kolcic, Ivana, Kumar, Ashish, Lind, Lars, Melén, Erik, Musk, Arthur W, Navarro, Pau, Nickle, David C, Padmanabhan, Sandosh, Raitakari, Olli T, Ried, Janina S, Ripatti, Samuli, Schulz, Holger, Scott, Robert A, Sin, Don D, Starr, John M, Viñuela, Ana, Völzke, Henry, Wild, Sarah H, Wright, Alan F, Zemunik, Tatijana, Jarvis, Deborah L, Spector, Tim D, Evans, David M, Lehtimäki, Terho, Vitart, Veronique, Kähönen, Mika, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Karrasch, Stefan, Probst-Hensch, Nicole M, Heinrich, Joachim, Stubbe, Beate, Wilson, James F, Wareham, Nicholas J, James, Alan L, Morris, Andrew P, Jarvelin, Marjo-Riitta, Hayward, Caroline, Sayers, Ian, Strachan, David P, Hall, Ian P, and Tobin, Martin D
Abstract: Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
Published: 2015
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37. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

Author: Arking, Dan E, Pulit, Sara L, Crotti, Lia, van der Harst, Pim, Munroe, Patricia B, Koopmann, Tamara T, Sotoodehnia, Nona, Rossin, Elizabeth J, Morley, Michael, Wang, Xinchen, Johnson, Andrew D, Lundby, Alicia, Gudbjartsson, Daníel F, Noseworthy, Peter A, Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V, Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M, Nolte, Ilja M, Smith, Albert Vernon, Bis, Joshua C, Isaacs, Aaron, Newhouse, Stephen J, Evans, Daniel S, Post, Wendy S, Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A, Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J, Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W, Naluai, Asa T, Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G, Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A, Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D, Harris, Tamara B, Launer, Lenore J, Shuldiner, Alan R, Alonso, Alvaro, Bader, Joel S, Ehret, Georg, Huang, Hailiang, Kao, W H Linda, Strait, James B, Macfarlane, Peter W, Brown, Morris, Caulfield, Mark J, Samani, Nilesh J, Kronenberg, Florian, Willeit, Johann, Smith, J Gustav, Greiser, Karin H, Meyer Zu Schwabedissen, Henriette, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R, Psaty, Bruce M, Rotter, Jerome I, Kolcic, Ivana, Polašek, Ozren, Wright, Alan F, Griffin, Maura, Daly, Mark J, Arnar, David O, Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C, Roden, Dan M, Zuvich, Rebecca L, Emilsson, Valur, Plump, Andrew S, Larson, Martin G, O'Donnell, Christopher J, Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R, Nalls, Michael A, Jula, Antti, Kontula, Kimmo K, Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M, den Hoed, Marcel, Loos, Ruth J F, Thelle, Dag S, Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F, Waldenberger, Melanie, de Boer, Rudolf A, Franke, Lude, van der Vleuten, Pieter A, Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A M, Behr, Elijah R, Dalageorgou, Chrysoula, Giudicessi, John R, Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M, Scherer, Stephen W, Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E, Greco M, Fabiola Del, Fuchsberger, Christian, O'Connell, Jeffrey R, Lee, Wai K, Watt, Graham C M, Campbell, Harry, Wild, Sarah H, El Mokhtari, Nour E, Frey, Norbert, Asselbergs, Folkert W, Mateo Leach, Irene, Navis, Gerjan, van den Berg, Maarten P, van Veldhuisen, Dirk J, Kellis, Manolis, Krijthe, Bouwe P, Franco, Oscar H, Hofman, Albert, Kors, Jan A, Uitterlinden, André G, Witteman, Jacqueline C M, Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A, Abecasis, Gonçalo R, Lakatta, Edward G, Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R P, Völker, Uwe, Snieder, Harold, Spector, Timothy D, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T, Viikari, Jorma S, Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N, Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F, Nyberg, Fredrik, Whincup, Peter H, Hingorani, Aroon D, Schott, Jean-Jacques, Bezzina, Connie R, Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F, Rudan, Igor, Franke, Andre, Mühleisen, Thomas W, Pramstaller, Peter P, Lehtimäki, Terho J, Paterson, Andrew D, Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia M, Siscovick, David S, Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B, Sanna, Serena, Ritchie, Marylyn D, Stricker, Bruno H, Stefansson, Kari, Boyer, Laurie A, Cappola, Thomas P, Olsen, Jesper V, Lage, Kasper, Schwartz, Peter J, Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J, Pfeufer, Arne, de Bakker, Paul I W, Newton-Cheh, Christopher, Arking, Dan E, Pulit, Sara L, Crotti, Lia, van der Harst, Pim, Munroe, Patricia B, Koopmann, Tamara T, Sotoodehnia, Nona, Rossin, Elizabeth J, Morley, Michael, Wang, Xinchen, Johnson, Andrew D, Lundby, Alicia, Gudbjartsson, Daníel F, Noseworthy, Peter A, Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V, Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M, Nolte, Ilja M, Smith, Albert Vernon, Bis, Joshua C, Isaacs, Aaron, Newhouse, Stephen J, Evans, Daniel S, Post, Wendy S, Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A, Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J, Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W, Naluai, Asa T, Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G, Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A, Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D, Harris, Tamara B, Launer, Lenore J, Shuldiner, Alan R, Alonso, Alvaro, Bader, Joel S, Ehret, Georg, Huang, Hailiang, Kao, W H Linda, Strait, James B, Macfarlane, Peter W, Brown, Morris, Caulfield, Mark J, Samani, Nilesh J, Kronenberg, Florian, Willeit, Johann, Smith, J Gustav, Greiser, Karin H, Meyer Zu Schwabedissen, Henriette, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R, Psaty, Bruce M, Rotter, Jerome I, Kolcic, Ivana, Polašek, Ozren, Wright, Alan F, Griffin, Maura, Daly, Mark J, Arnar, David O, Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C, Roden, Dan M, Zuvich, Rebecca L, Emilsson, Valur, Plump, Andrew S, Larson, Martin G, O'Donnell, Christopher J, Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R, Nalls, Michael A, Jula, Antti, Kontula, Kimmo K, Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M, den Hoed, Marcel, Loos, Ruth J F, Thelle, Dag S, Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F, Waldenberger, Melanie, de Boer, Rudolf A, Franke, Lude, van der Vleuten, Pieter A, Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A M, Behr, Elijah R, Dalageorgou, Chrysoula, Giudicessi, John R, Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M, Scherer, Stephen W, Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E, Greco M, Fabiola Del, Fuchsberger, Christian, O'Connell, Jeffrey R, Lee, Wai K, Watt, Graham C M, Campbell, Harry, Wild, Sarah H, El Mokhtari, Nour E, Frey, Norbert, Asselbergs, Folkert W, Mateo Leach, Irene, Navis, Gerjan, van den Berg, Maarten P, van Veldhuisen, Dirk J, Kellis, Manolis, Krijthe, Bouwe P, Franco, Oscar H, Hofman, Albert, Kors, Jan A, Uitterlinden, André G, Witteman, Jacqueline C M, Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A, Abecasis, Gonçalo R, Lakatta, Edward G, Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R P, Völker, Uwe, Snieder, Harold, Spector, Timothy D, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T, Viikari, Jorma S, Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N, Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F, Nyberg, Fredrik, Whincup, Peter H, Hingorani, Aroon D, Schott, Jean-Jacques, Bezzina, Connie R, Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F, Rudan, Igor, Franke, Andre, Mühleisen, Thomas W, Pramstaller, Peter P, Lehtimäki, Terho J, Paterson, Andrew D, Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia M, Siscovick, David S, Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B, Sanna, Serena, Ritchie, Marylyn D, Stricker, Bruno H, Stefansson, Kari, Boyer, Laurie A, Cappola, Thomas P, Olsen, Jesper V, Lage, Kasper, Schwartz, Peter J, Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J, Pfeufer, Arne, de Bakker, Paul I W, and Newton-Cheh, Christopher
Abstract: The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
Published: 2014
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38. Evidence of Inbreeding Depression on Human Height

Author: McQuillan, Ruth, Eklund, Niina, Pirastu, Nicola, Kuningas, Maris, McEvoy, Brian P, Esko, Tõnu, Corre, Tanguy, Davies, Gail, Kaakinen, Marika, Lyytikäinen, Leo-Pekka, Kristiansson, Kati, Havulinna, Aki S, Gögele, Martin, Vitart, Veronique, Tenesa, Albert, Aulchenko, Yurii, Hayward, Caroline, Johansson, Åsa, Boban, Mladen, Ulivi, Sheila, Robino, Antonietta, Boraska, Vesna, Igl, Wilmar, Wild, Sarah H, Zgaga, Lina, Amin, Najaf, Theodoratou, Evropi, Polašek, Ozren, Girotto, Giorgia, Lopez, Lorna M, Sala, Cinzia, Lahti, Jari, Laatikainen, Tiina, Prokopenko, Inga, Kals, Mart, Viikari, Jorma, Yang, Jian, Pouta, Anneli, Estrada, Karol, Hofman, Albert, Freimer, Nelson, Martin, Nicholas G, Kähönen, Mika, Milani, Lili, Heliövaara, Markku, Vartiainen, Erkki, Räikkönen, Katri, Masciullo, Corrado, Starr, John M, Hicks, Andrew A, Esposito, Laura, Kolčić, Ivana, Farrington, Susan M, Oostra, Ben, Zemunik, Tatijana, Campbell, Harry, Kirin, Mirna, Pehlic, Marina, Faletra, Flavio, Porteous, David, Pistis, Giorgio, Widén, Elisabeth, Salomaa, Veikko, Koskinen, Seppo, Fischer, Krista, Lehtimäki, Terho, Heath, Andrew, McCarthy, Mark I, Rivadeneira, Fernando, Montgomery, Grant W, Tiemeier, Henning, Hartikainen, Anna-Liisa, Madden, Pamela A F, d'Adamo, Pio, Hastie, Nicholas D, Gyllensten, Ulf, Wright, Alan F, van Duijn, Cornelia M, Dunlop, Malcolm, Rudan, Igor, Gasparini, Paolo, Pramstaller, Peter P, Deary, Ian J, Toniolo, Daniela, Eriksson, Johan G, Jula, Antti, Raitakari, Olli T, Metspalu, Andres, Perola, Markus, Järvelin, Marjo-Riitta, Uitterlinden, André, Visscher, Peter M, Wilson, James F, McQuillan, Ruth, Eklund, Niina, Pirastu, Nicola, Kuningas, Maris, McEvoy, Brian P, Esko, Tõnu, Corre, Tanguy, Davies, Gail, Kaakinen, Marika, Lyytikäinen, Leo-Pekka, Kristiansson, Kati, Havulinna, Aki S, Gögele, Martin, Vitart, Veronique, Tenesa, Albert, Aulchenko, Yurii, Hayward, Caroline, Johansson, Åsa, Boban, Mladen, Ulivi, Sheila, Robino, Antonietta, Boraska, Vesna, Igl, Wilmar, Wild, Sarah H, Zgaga, Lina, Amin, Najaf, Theodoratou, Evropi, Polašek, Ozren, Girotto, Giorgia, Lopez, Lorna M, Sala, Cinzia, Lahti, Jari, Laatikainen, Tiina, Prokopenko, Inga, Kals, Mart, Viikari, Jorma, Yang, Jian, Pouta, Anneli, Estrada, Karol, Hofman, Albert, Freimer, Nelson, Martin, Nicholas G, Kähönen, Mika, Milani, Lili, Heliövaara, Markku, Vartiainen, Erkki, Räikkönen, Katri, Masciullo, Corrado, Starr, John M, Hicks, Andrew A, Esposito, Laura, Kolčić, Ivana, Farrington, Susan M, Oostra, Ben, Zemunik, Tatijana, Campbell, Harry, Kirin, Mirna, Pehlic, Marina, Faletra, Flavio, Porteous, David, Pistis, Giorgio, Widén, Elisabeth, Salomaa, Veikko, Koskinen, Seppo, Fischer, Krista, Lehtimäki, Terho, Heath, Andrew, McCarthy, Mark I, Rivadeneira, Fernando, Montgomery, Grant W, Tiemeier, Henning, Hartikainen, Anna-Liisa, Madden, Pamela A F, d'Adamo, Pio, Hastie, Nicholas D, Gyllensten, Ulf, Wright, Alan F, van Duijn, Cornelia M, Dunlop, Malcolm, Rudan, Igor, Gasparini, Paolo, Pramstaller, Peter P, Deary, Ian J, Toniolo, Daniela, Eriksson, Johan G, Jula, Antti, Raitakari, Olli T, Metspalu, Andres, Perola, Markus, Järvelin, Marjo-Riitta, Uitterlinden, André, Visscher, Peter M, and Wilson, James F
Abstract: Stature is a classical and highly heritable complex trait, with 80%–90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ2 = 83.89, df = 1; p = 5.2×10−20). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.
Published: 2012
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39. Evidence of Inbreeding Depression on Human Height

Author: McQuillan, Ruth, Eklund, Niina, Pirastu, Nicola, Kuningas, Maris, McEvoy, Brian P, Esko, Tõnu, Corre, Tanguy, Davies, Gail, Kaakinen, Marika, Lyytikäinen, Leo-Pekka, Kristiansson, Kati, Havulinna, Aki S, Gögele, Martin, Vitart, Veronique, Tenesa, Albert, Aulchenko, Yurii, Hayward, Caroline, Johansson, Åsa, Boban, Mladen, Ulivi, Sheila, Robino, Antonietta, Boraska, Vesna, Igl, Wilmar, Wild, Sarah H, Zgaga, Lina, Amin, Najaf, Theodoratou, Evropi, Polašek, Ozren, Girotto, Giorgia, Lopez, Lorna M, Sala, Cinzia, Lahti, Jari, Laatikainen, Tiina, Prokopenko, Inga, Kals, Mart, Viikari, Jorma, Yang, Jian, Pouta, Anneli, Estrada, Karol, Hofman, Albert, Freimer, Nelson, Martin, Nicholas G, Kähönen, Mika, Milani, Lili, Heliövaara, Markku, Vartiainen, Erkki, Räikkönen, Katri, Masciullo, Corrado, Starr, John M, Hicks, Andrew A, Esposito, Laura, Kolčić, Ivana, Farrington, Susan M, Oostra, Ben, Zemunik, Tatijana, Campbell, Harry, Kirin, Mirna, Pehlic, Marina, Faletra, Flavio, Porteous, David, Pistis, Giorgio, Widén, Elisabeth, Salomaa, Veikko, Koskinen, Seppo, Fischer, Krista, Lehtimäki, Terho, Heath, Andrew, McCarthy, Mark I, Rivadeneira, Fernando, Montgomery, Grant W, Tiemeier, Henning, Hartikainen, Anna-Liisa, Madden, Pamela A F, d'Adamo, Pio, Hastie, Nicholas D, Gyllensten, Ulf, Wright, Alan F, van Duijn, Cornelia M, Dunlop, Malcolm, Rudan, Igor, Gasparini, Paolo, Pramstaller, Peter P, Deary, Ian J, Toniolo, Daniela, Eriksson, Johan G, Jula, Antti, Raitakari, Olli T, Metspalu, Andres, Perola, Markus, Järvelin, Marjo-Riitta, Uitterlinden, André, Visscher, Peter M, Wilson, James F, McQuillan, Ruth, Eklund, Niina, Pirastu, Nicola, Kuningas, Maris, McEvoy, Brian P, Esko, Tõnu, Corre, Tanguy, Davies, Gail, Kaakinen, Marika, Lyytikäinen, Leo-Pekka, Kristiansson, Kati, Havulinna, Aki S, Gögele, Martin, Vitart, Veronique, Tenesa, Albert, Aulchenko, Yurii, Hayward, Caroline, Johansson, Åsa, Boban, Mladen, Ulivi, Sheila, Robino, Antonietta, Boraska, Vesna, Igl, Wilmar, Wild, Sarah H, Zgaga, Lina, Amin, Najaf, Theodoratou, Evropi, Polašek, Ozren, Girotto, Giorgia, Lopez, Lorna M, Sala, Cinzia, Lahti, Jari, Laatikainen, Tiina, Prokopenko, Inga, Kals, Mart, Viikari, Jorma, Yang, Jian, Pouta, Anneli, Estrada, Karol, Hofman, Albert, Freimer, Nelson, Martin, Nicholas G, Kähönen, Mika, Milani, Lili, Heliövaara, Markku, Vartiainen, Erkki, Räikkönen, Katri, Masciullo, Corrado, Starr, John M, Hicks, Andrew A, Esposito, Laura, Kolčić, Ivana, Farrington, Susan M, Oostra, Ben, Zemunik, Tatijana, Campbell, Harry, Kirin, Mirna, Pehlic, Marina, Faletra, Flavio, Porteous, David, Pistis, Giorgio, Widén, Elisabeth, Salomaa, Veikko, Koskinen, Seppo, Fischer, Krista, Lehtimäki, Terho, Heath, Andrew, McCarthy, Mark I, Rivadeneira, Fernando, Montgomery, Grant W, Tiemeier, Henning, Hartikainen, Anna-Liisa, Madden, Pamela A F, d'Adamo, Pio, Hastie, Nicholas D, Gyllensten, Ulf, Wright, Alan F, van Duijn, Cornelia M, Dunlop, Malcolm, Rudan, Igor, Gasparini, Paolo, Pramstaller, Peter P, Deary, Ian J, Toniolo, Daniela, Eriksson, Johan G, Jula, Antti, Raitakari, Olli T, Metspalu, Andres, Perola, Markus, Järvelin, Marjo-Riitta, Uitterlinden, André, Visscher, Peter M, and Wilson, James F
Abstract: Stature is a classical and highly heritable complex trait, with 80%–90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ2 = 83.89, df = 1; p = 5.2×10−20). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.
Published: 2012
Full Text: View/download PDF

40. Evidence of Inbreeding Depression on Human Height

Author: McQuillan, Ruth, Eklund, Niina, Pirastu, Nicola, Kuningas, Maris, McEvoy, Brian P, Esko, Tõnu, Corre, Tanguy, Davies, Gail, Kaakinen, Marika, Lyytikäinen, Leo-Pekka, Kristiansson, Kati, Havulinna, Aki S, Gögele, Martin, Vitart, Veronique, Tenesa, Albert, Aulchenko, Yurii, Hayward, Caroline, Johansson, Åsa, Boban, Mladen, Ulivi, Sheila, Robino, Antonietta, Boraska, Vesna, Igl, Wilmar, Wild, Sarah H, Zgaga, Lina, Amin, Najaf, Theodoratou, Evropi, Polašek, Ozren, Girotto, Giorgia, Lopez, Lorna M, Sala, Cinzia, Lahti, Jari, Laatikainen, Tiina, Prokopenko, Inga, Kals, Mart, Viikari, Jorma, Yang, Jian, Pouta, Anneli, Estrada, Karol, Hofman, Albert, Freimer, Nelson, Martin, Nicholas G, Kähönen, Mika, Milani, Lili, Heliövaara, Markku, Vartiainen, Erkki, Räikkönen, Katri, Masciullo, Corrado, Starr, John M, Hicks, Andrew A, Esposito, Laura, Kolčić, Ivana, Farrington, Susan M, Oostra, Ben, Zemunik, Tatijana, Campbell, Harry, Kirin, Mirna, Pehlic, Marina, Faletra, Flavio, Porteous, David, Pistis, Giorgio, Widén, Elisabeth, Salomaa, Veikko, Koskinen, Seppo, Fischer, Krista, Lehtimäki, Terho, Heath, Andrew, McCarthy, Mark I, Rivadeneira, Fernando, Montgomery, Grant W, Tiemeier, Henning, Hartikainen, Anna-Liisa, Madden, Pamela A F, d'Adamo, Pio, Hastie, Nicholas D, Gyllensten, Ulf, Wright, Alan F, van Duijn, Cornelia M, Dunlop, Malcolm, Rudan, Igor, Gasparini, Paolo, Pramstaller, Peter P, Deary, Ian J, Toniolo, Daniela, Eriksson, Johan G, Jula, Antti, Raitakari, Olli T, Metspalu, Andres, Perola, Markus, Järvelin, Marjo-Riitta, Uitterlinden, André, Visscher, Peter M, Wilson, James F, McQuillan, Ruth, Eklund, Niina, Pirastu, Nicola, Kuningas, Maris, McEvoy, Brian P, Esko, Tõnu, Corre, Tanguy, Davies, Gail, Kaakinen, Marika, Lyytikäinen, Leo-Pekka, Kristiansson, Kati, Havulinna, Aki S, Gögele, Martin, Vitart, Veronique, Tenesa, Albert, Aulchenko, Yurii, Hayward, Caroline, Johansson, Åsa, Boban, Mladen, Ulivi, Sheila, Robino, Antonietta, Boraska, Vesna, Igl, Wilmar, Wild, Sarah H, Zgaga, Lina, Amin, Najaf, Theodoratou, Evropi, Polašek, Ozren, Girotto, Giorgia, Lopez, Lorna M, Sala, Cinzia, Lahti, Jari, Laatikainen, Tiina, Prokopenko, Inga, Kals, Mart, Viikari, Jorma, Yang, Jian, Pouta, Anneli, Estrada, Karol, Hofman, Albert, Freimer, Nelson, Martin, Nicholas G, Kähönen, Mika, Milani, Lili, Heliövaara, Markku, Vartiainen, Erkki, Räikkönen, Katri, Masciullo, Corrado, Starr, John M, Hicks, Andrew A, Esposito, Laura, Kolčić, Ivana, Farrington, Susan M, Oostra, Ben, Zemunik, Tatijana, Campbell, Harry, Kirin, Mirna, Pehlic, Marina, Faletra, Flavio, Porteous, David, Pistis, Giorgio, Widén, Elisabeth, Salomaa, Veikko, Koskinen, Seppo, Fischer, Krista, Lehtimäki, Terho, Heath, Andrew, McCarthy, Mark I, Rivadeneira, Fernando, Montgomery, Grant W, Tiemeier, Henning, Hartikainen, Anna-Liisa, Madden, Pamela A F, d'Adamo, Pio, Hastie, Nicholas D, Gyllensten, Ulf, Wright, Alan F, van Duijn, Cornelia M, Dunlop, Malcolm, Rudan, Igor, Gasparini, Paolo, Pramstaller, Peter P, Deary, Ian J, Toniolo, Daniela, Eriksson, Johan G, Jula, Antti, Raitakari, Olli T, Metspalu, Andres, Perola, Markus, Järvelin, Marjo-Riitta, Uitterlinden, André, Visscher, Peter M, and Wilson, James F
Abstract: Stature is a classical and highly heritable complex trait, with 80%–90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ2 = 83.89, df = 1; p = 5.2×10−20). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.
Published: 2012
Full Text: View/download PDF

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