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2. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

University of Helsinki, Hospital for Children and Adolescents, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Institute of Behavioural Sciences, University of Helsinki, Clinicum, University of Helsinki, Hjelt Institute, Ried, Janina S., Jeff, Janina M., Chu, Audrey Y., Bragg-Gresham, Jennifer L., van Dongen, Jenny, Huffman, Jennifer E., Ahluwalia, Tarunveer S., Cadby, Gemma, Eklund, Niina, Eriksson, Joel, Esko, Tonu, Feitosa, Mary F., Goel, Anuj, Gorski, Mathias, Hayward, Caroline, Heard-Costa, Nancy L., Jackson, Anne U., Jokinen, Eero, Kanoni, Stavroula, Kristiansson, Kati, Kutalik, Zoltan, Lahti, Jari, Luan, Jian'an, Maegi, Reedik, Mahajan, Anubha, Mangino, Massimo, Medina-Gomez, Carolina, Monda, Keri L., Nolte, Ilja M., Perusse, Louis, Prokopenko, Inga, Qi, Lu, Rose, Lynda M., Salvi, Erika, Smith, Megan T., Snieder, Harold, Stancakova, Alena, Sung, Yun Ju, Tachmazidou, Ioanna, Teumer, Alexander, Thorleifsson, Gudmar, van der Harst, Pim, Walker, Ryan W., Wang, Sophie R., Wild, Sarah H., Willems, Sara M., Wong, Andrew, Zhang, Weihua, Albrecht, Eva, Alves, Alexessander Couto, Bakker, Stephan J. L., Barlassina, Cristina, Bartz, Traci M., Beilby, John, Bellis, Claire, Bergman, Richard N., Bergmann, Sven, Blangero, John, Blueher, Matthias, Boerwinkle, Eric, Bonnycastle, Lori L., Bornstein, Stefan R., Bruinenberg, Marcel, Campbell, Harry, Chen, Yii-Der Ida, Chiang, Charleston W. K., Chines, Peter S., Collins, Francis S., Cucca, Fracensco, Cupples, L. Adrienne, D'Avila, Francesca, de Geus, Eco J. C., Dedoussis, George, Dimitriou, Maria, Doering, Angela, Eriksson, Johan G., Farmaki, Aliki-Eleni, Farrall, Martin, Ferreira, Teresa, Fischer, Krista, Forouhi, Nita G., Friedrich, Nele, Gjesing, Anette Prior, Glorioso, Nicola, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Graessler, Juergen, Grewal, Jagvir, Hamsten, Anders, Harder, Marie Neergaard, Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew Tym, Havulinna, Aki S., Heliovaara, Markku, Hillege, Hans, Hofman, Albert, Holmen, Oddgeir, Homuth, Georg, Hottenga, Jouke-Jan, Hui, Jennie, Husemoen, Lise Lotte, Hysi, Pirro G., Isaacs, Aaron, Ittermann, Till, Jalilzadeh, Shapour, James, Alan L., Jorgensen, Torben, Jousilahti, Pekka, Jula, Antti, Justesen, Johanne Marie, Justice, Anne E., Kahonen, Mika, Karaleftheri, Maria, Khaw, Kay Tee, Keinanen-Kiukaanniemi, Sirkka M., Kinnunen, Leena, Knekt, Paul B., Koistinen, Heikki A., Kolcic, Ivana, Kooner, Ishminder K., Koskinen, Seppo, Kovacs, Peter, Kyriakou, Theodosios, Laitinen, Tomi, Langenberg, Claudia, Lewin, Alexandra M., Lichtner, Peter, Lindgren, Cecilia M., Lindstrom, Jaana, Linneberg, Allan, Lorbeer, Roberto, Lorentzon, Mattias, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Manunta, Paolo, Leach, Irene Mateo, McArdle, Wendy L., Mcknight, Barbara, Mohlke, Karen L., Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Montasser, May E., Morris, Andrew P., Mueller, Gabriele, Musk, Arthur W., Narisu, Narisu, Ong, Ken K., Oostra, Ben A., Osmond, Clive, Palotie, Aarno, Pankow, James S., Paternoster, Lavinia, Penninx, Brenda W., Pichler, Irene, Pilia, Maria G., Polasek, Ozren, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rayner, Nigel W., Ribel-Madsen, Rasmus, Rice, Treva K., Richards, Marcus, Ridker, Paul M., Rivadeneira, Fernando, Ryan, Kathy A., Sanna, Serena, Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Sebert, Sylvain, Southam, Lorraine, Sparso, Thomas Hempel, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stolk, Ronald P., Strauch, Konstantin, Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Toenjes, Anke, Tsafantakis, Emmanouil, van der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Vandenput, Liesbeth, Vartiainen, Erkki, Venturini, Cristina, Verweij, Niek, Viikari, Jorma S., Vitart, Veronique, Vohl, Marie-Claude, Vonk, Judith M., Waeber, Gerard, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Winkler, Thomas W., Wright, Alan F., Yerges-Armstrong, Laura M., Zhao, Jing Hua, Zillikens, M. Carola, Boomsma, Dorret I., Bouchard, Claude, Chambers, John C., Chasman, Daniel I., Cusi, Daniele, Gansevoort, Ron T., Gieger, Christian, Hansen, Torben, Hicks, Andrew A., Hu, Frank, Hveem, Kristian, Jarvelin, Marjo-Riitta, Kajantie, Eero, Kooner, Jaspal S., Kuh, Diana, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lehtimaeki, Terho, Metspalu, Andres, Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Palmer, Lyle J., Pedersen, Oluf, Perola, Markus, Peters, Annette, Psaty, Bruce M., Puolijoki, Hannu, Rauramaa, Rainer, Rudan, Igor, Salomaa, Veikko, Schwarz, Peter E. H., Shudiner, Alan R., Smit, Jan H., Sorensen, Thorkild I. A., Spector, Timothy D., Stefansson, Kari, Stumvoll, Michael, Tremblay, Angelo, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Voelker, Uwe, Vollenweider, Peter, Wareham, Nicholas J., Watkins, Hugh, Wilson, James F., Zeggini, Eleftheria, Abecasis, Goncalo R., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, van Duijn, Cornelia M., Fox, Caroline, Groop, Leif C., Heid, Iris M., Hunter, David J., Kaplan, Robert C., McCarthy, Mark I., North, Kari E., O'Connell, Jeffrey R., Schlessinger, David, Thorsteinsdottir, Unnur, Strachan, David P., Frayling, Timothy, Hirschhorn, Joel N., Mueller-Nurasyid, Martina, Loos, Ruth J. F., University of Helsinki, Hospital for Children and Adolescents, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Institute of Behavioural Sciences, University of Helsinki, Clinicum, University of Helsinki, Hjelt Institute, Ried, Janina S., Jeff, Janina M., Chu, Audrey Y., Bragg-Gresham, Jennifer L., van Dongen, Jenny, Huffman, Jennifer E., Ahluwalia, Tarunveer S., Cadby, Gemma, Eklund, Niina, Eriksson, Joel, Esko, Tonu, Feitosa, Mary F., Goel, Anuj, Gorski, Mathias, Hayward, Caroline, Heard-Costa, Nancy L., Jackson, Anne U., Jokinen, Eero, Kanoni, Stavroula, Kristiansson, Kati, Kutalik, Zoltan, Lahti, Jari, Luan, Jian'an, Maegi, Reedik, Mahajan, Anubha, Mangino, Massimo, Medina-Gomez, Carolina, Monda, Keri L., Nolte, Ilja M., Perusse, Louis, Prokopenko, Inga, Qi, Lu, Rose, Lynda M., Salvi, Erika, Smith, Megan T., Snieder, Harold, Stancakova, Alena, Sung, Yun Ju, Tachmazidou, Ioanna, Teumer, Alexander, Thorleifsson, Gudmar, van der Harst, Pim, Walker, Ryan W., Wang, Sophie R., Wild, Sarah H., Willems, Sara M., Wong, Andrew, Zhang, Weihua, Albrecht, Eva, Alves, Alexessander Couto, Bakker, Stephan J. L., Barlassina, Cristina, Bartz, Traci M., Beilby, John, Bellis, Claire, Bergman, Richard N., Bergmann, Sven, Blangero, John, Blueher, Matthias, Boerwinkle, Eric, Bonnycastle, Lori L., Bornstein, Stefan R., Bruinenberg, Marcel, Campbell, Harry, Chen, Yii-Der Ida, Chiang, Charleston W. K., Chines, Peter S., Collins, Francis S., Cucca, Fracensco, Cupples, L. Adrienne, D'Avila, Francesca, de Geus, Eco J. C., Dedoussis, George, Dimitriou, Maria, Doering, Angela, Eriksson, Johan G., Farmaki, Aliki-Eleni, Farrall, Martin, Ferreira, Teresa, Fischer, Krista, Forouhi, Nita G., Friedrich, Nele, Gjesing, Anette Prior, Glorioso, Nicola, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Graessler, Juergen, Grewal, Jagvir, Hamsten, Anders, Harder, Marie Neergaard, Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew Tym, Havulinna, Aki S., Heliovaara, Markku, Hillege, Hans, Hofman, Albert, Holmen, Oddgeir, Homuth, Georg, Hottenga, Jouke-Jan, Hui, Jennie, Husemoen, Lise Lotte, Hysi, Pirro G., Isaacs, Aaron, Ittermann, Till, Jalilzadeh, Shapour, James, Alan L., Jorgensen, Torben, Jousilahti, Pekka, Jula, Antti, Justesen, Johanne Marie, Justice, Anne E., Kahonen, Mika, Karaleftheri, Maria, Khaw, Kay Tee, Keinanen-Kiukaanniemi, Sirkka M., Kinnunen, Leena, Knekt, Paul B., Koistinen, Heikki A., Kolcic, Ivana, Kooner, Ishminder K., Koskinen, Seppo, Kovacs, Peter, Kyriakou, Theodosios, Laitinen, Tomi, Langenberg, Claudia, Lewin, Alexandra M., Lichtner, Peter, Lindgren, Cecilia M., Lindstrom, Jaana, Linneberg, Allan, Lorbeer, Roberto, Lorentzon, Mattias, Luben, Robert, Lyssenko, Valeriya, Mannisto, Satu, Manunta, Paolo, Leach, Irene Mateo, McArdle, Wendy L., Mcknight, Barbara, Mohlke, Karen L., Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Montasser, May E., Morris, Andrew P., Mueller, Gabriele, Musk, Arthur W., Narisu, Narisu, Ong, Ken K., Oostra, Ben A., Osmond, Clive, Palotie, Aarno, Pankow, James S., Paternoster, Lavinia, Penninx, Brenda W., Pichler, Irene, Pilia, Maria G., Polasek, Ozren, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rayner, Nigel W., Ribel-Madsen, Rasmus, Rice, Treva K., Richards, Marcus, Ridker, Paul M., Rivadeneira, Fernando, Ryan, Kathy A., Sanna, Serena, Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Sebert, Sylvain, Southam, Lorraine, Sparso, Thomas Hempel, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stolk, Ronald P., Strauch, Konstantin, Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Toenjes, Anke, Tsafantakis, Emmanouil, van der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Vandenput, Liesbeth, Vartiainen, Erkki, Venturini, Cristina, Verweij, Niek, Viikari, Jorma S., Vitart, Veronique, Vohl, Marie-Claude, Vonk, Judith M., Waeber, Gerard, Widen, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Winkler, Thomas W., Wright, Alan F., Yerges-Armstrong, Laura M., Zhao, Jing Hua, Zillikens, M. Carola, Boomsma, Dorret I., Bouchard, Claude, Chambers, John C., Chasman, Daniel I., Cusi, Daniele, Gansevoort, Ron T., Gieger, Christian, Hansen, Torben, Hicks, Andrew A., Hu, Frank, Hveem, Kristian, Jarvelin, Marjo-Riitta, Kajantie, Eero, Kooner, Jaspal S., Kuh, Diana, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lehtimaeki, Terho, Metspalu, Andres, Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Palmer, Lyle J., Pedersen, Oluf, Perola, Markus, Peters, Annette, Psaty, Bruce M., Puolijoki, Hannu, Rauramaa, Rainer, Rudan, Igor, Salomaa, Veikko, Schwarz, Peter E. H., Shudiner, Alan R., Smit, Jan H., Sorensen, Thorkild I. A., Spector, Timothy D., Stefansson, Kari, Stumvoll, Michael, Tremblay, Angelo, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, Voelker, Uwe, Vollenweider, Peter, Wareham, Nicholas J., Watkins, Hugh, Wilson, James F., Zeggini, Eleftheria, Abecasis, Goncalo R., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, van Duijn, Cornelia M., Fox, Caroline, Groop, Leif C., Heid, Iris M., Hunter, David J., Kaplan, Robert C., McCarthy, Mark I., North, Kari E., O'Connell, Jeffrey R., Schlessinger, David, Thorsteinsdottir, Unnur, Strachan, David P., Frayling, Timothy, Hirschhorn, Joel N., Mueller-Nurasyid, Martina, and Loos, Ruth J. F.

Abstract

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

Published
2016

3. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Ried, Janina S, Jeff M, Janina, Chu, Audrey Y, Bragg-Gresham, Jennifer L, van Dongen, Jenny, Huffman, Jennifer E, Ahluwalia, Tarun Veer Singh, Cadby, Gemma, Eklund, Niina, Eriksson, Joel, Esko, Tõnu, Feitosa, Mary F, Goel, Anuj, Gorski, Mathias, Hayward, Caroline, Heard-Costa, Nancy L, Jackson, Anne U, Jokinen, Eero, Kanoni, Stavroula, Kristiansson, Kati, Kutalik, Zoltán, Lahti, Jari, Luan, Jian'an, Mägi, Reedik, Mahajan, Anubha, Mangino, Massimo, Medina-Gomez, Carolina, Monda, Keri L, Nolte, Ilja M, Pérusse, Louis, Prokopenko, Inga, Qi, Lu, Rose, Lynda M, Salvi, Erika, Smith, Megan T, Snieder, Harold, Stančáková, Alena, Ju Sung, Yun, Tachmazidou, Ioanna, Teumer, Alexander, Thorleifsson, Gudmar, van der Harst, Pim, Walker, Ryan W, Wang, Sophie R, Wild, Sarah H, Willems, Sara M, Wong, Andrew, Zhang, Weihua, Albrecht, Eva, Couto Alves, Alexessander, Bakker, Stephan J L, Barlassina, Cristina, Bartz, Traci M, Beilby, John, Bellis, Claire, Bergman, Richard N, Bergmann, Sven, Blangero, John, Blüher, Matthias, Boerwinkle, Eric, Bonnycastle, Lori L, Bornstein, Stefan R, Bruinenberg, Marcel, Campbell, Harry, Chen, Yii-Der Ida, Chiang, Charleston W K, Chines, Peter S, Collins, Francis S, Cucca, Fracensco, Cupples, L Adrienne, D'Avila, Francesca, de Geus, Eco J C, Dedoussis, George, Dimitriou, Maria, Döring, Angela, Eriksson, Johan G, Farmaki, Aliki-Eleni, Farrall, Martin, Ferreira, Teresa, Fischer, Krista, Forouhi, Nita G, Friedrich, Nele, Gjesing, Anette Marianne Prior, Glorioso, Nicola, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Gräßler, Jürgen, Grewal, Jagvir, Hamsten, Anders, Harder, Marie Neergaard, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew Tym, Havulinna, Aki S, Heliövaara, Markku, Hillege, Hans, Hofman, Albert, Holmen, Oddgeir, Homuth, Georg, Hottenga, Jouke-Jan, Hui, Jennie, Husemoen, Lise Lotte, Hysi, Pirro G, Isaacs, Aaron, Ittermann, Till, Jalilzadeh, Shapour, James, Alan L, Jørgensen, Torben, Jousilahti, Pekka, Jula, Antti, Marie Justesen, Johanne, Justice, Anne E, Kähönen, Mika, Karaleftheri, Maria, Tee Khaw, Kay, Keinanen-Kiukaanniemi, Sirkka M, Kinnunen, Leena, Knekt, Paul B, Koistinen, Heikki A, Kolcic, Ivana, Kooner, Ishminder K, Koskinen, Seppo, Kovacs, Peter, Kyriakou, Theodosios, Laitinen, Tomi, Langenberg, Claudia, Lewin, Alexandra M, Lichtner, Peter, Lindgren, Cecilia M, Lindström, Jaana, Linneberg, Allan, Lorbeer, Roberto, Lorentzon, Mattias, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Manunta, Paolo, Leach, Irene Mateo, McArdle, Wendy L, Mcknight, Barbara, Mohlke, Karen L, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Montasser, May E, Morris, Andrew P, Müller, Gabriele, Musk, Arthur W, Narisu, Narisu, Ong, Ken K, Oostra, Ben A, Osmond, Clive, Palotie, Aarno, Pankow, James S, Paternoster, Lavinia, Penninx, Brenda W, Pichler, Irene, Pilia, Maria G, Polašek, Ozren, Pramstaller, Peter P, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rayner, Nigel W, Ribel-Madsen, Rasmus, Rice, Treva K, Richards, Marcus, Ridker, Paul M, Rivadeneira, Fernando, Ryan, Kathy A, Sanna, Serena, Sarzynski, Mark A, Scholtens, Salome, Scott, Robert A, Sebert, Sylvain, Southam, Lorraine, Sparsø, Thomas Hempel, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stolk, Ronald P, Strauch, Konstantin, Stringham, Heather M, Swertz, Morris A, Swift, Amy J, Tönjes, Anke, Tsafantakis, Emmanouil, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vandenput, Liesbeth, Vartiainen, Erkki, Venturini, Cristina, Verweij, Niek, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Vonk, Judith M, Waeber, Gérard, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Winkler, Thomas W, Wright, Alan F, Yerges-Armstrong, Laura M, Hua Zhao, Jing, Carola Zillikens, M, Boomsma, Dorret I, Bouchard, Claude, Chambers, John C, Chasman, Daniel I, Cusi, Daniele, Gansevoort, Ron T, Gieger, Christian, Hansen, Torben, Hicks, Andrew A, Hu, Frank, Hveem, Kristian, Jarvelin, Marjo-Riitta, Kajantie, Eero, Kooner, Jaspal S, Kuh, Diana, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lehtimäki, Terho, Metspalu, Andres, Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J, Palmer, Lyle J, Pedersen, Oluf, Perola, Markus, Peters, Annette, Psaty, Bruce M, Puolijoki, Hannu, Rauramaa, Rainer, Rudan, Igor, Salomaa, Veikko, Schwarz, Peter E H, Shudiner, Alan R, Smit, Jan H, Sørensen, Thorkild I A, Spector, Timothy D, Stefansson, Kari, Stumvoll, Michael, Tremblay, Angelo, Tuomilehto, Jaakko, Uitterlinden, André G, Uusitupa, Matti, Völker, Uwe, Vollenweider, Peter, Wareham, Nicholas J, Watkins, Hugh, Wilson, James F, Zeggini, Eleftheria, Abecasis, Goncalo R, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, van Duijn, Cornelia M, Fox, Caroline, Groop, Leif C, Heid, Iris M, Hunter, David J, Kaplan, Robert C, McCarthy, Mark I, North, Kari E, O'Connell, Jeffrey R, Schlessinger, David, Thorsteinsdottir, Unnur, Strachan, David P, Frayling, Timothy, Hirschhorn, Joel N, Müller-Nurasyid, Martina, Loos, Ruth J F, Ried, Janina S, Jeff M, Janina, Chu, Audrey Y, Bragg-Gresham, Jennifer L, van Dongen, Jenny, Huffman, Jennifer E, Ahluwalia, Tarun Veer Singh, Cadby, Gemma, Eklund, Niina, Eriksson, Joel, Esko, Tõnu, Feitosa, Mary F, Goel, Anuj, Gorski, Mathias, Hayward, Caroline, Heard-Costa, Nancy L, Jackson, Anne U, Jokinen, Eero, Kanoni, Stavroula, Kristiansson, Kati, Kutalik, Zoltán, Lahti, Jari, Luan, Jian'an, Mägi, Reedik, Mahajan, Anubha, Mangino, Massimo, Medina-Gomez, Carolina, Monda, Keri L, Nolte, Ilja M, Pérusse, Louis, Prokopenko, Inga, Qi, Lu, Rose, Lynda M, Salvi, Erika, Smith, Megan T, Snieder, Harold, Stančáková, Alena, Ju Sung, Yun, Tachmazidou, Ioanna, Teumer, Alexander, Thorleifsson, Gudmar, van der Harst, Pim, Walker, Ryan W, Wang, Sophie R, Wild, Sarah H, Willems, Sara M, Wong, Andrew, Zhang, Weihua, Albrecht, Eva, Couto Alves, Alexessander, Bakker, Stephan J L, Barlassina, Cristina, Bartz, Traci M, Beilby, John, Bellis, Claire, Bergman, Richard N, Bergmann, Sven, Blangero, John, Blüher, Matthias, Boerwinkle, Eric, Bonnycastle, Lori L, Bornstein, Stefan R, Bruinenberg, Marcel, Campbell, Harry, Chen, Yii-Der Ida, Chiang, Charleston W K, Chines, Peter S, Collins, Francis S, Cucca, Fracensco, Cupples, L Adrienne, D'Avila, Francesca, de Geus, Eco J C, Dedoussis, George, Dimitriou, Maria, Döring, Angela, Eriksson, Johan G, Farmaki, Aliki-Eleni, Farrall, Martin, Ferreira, Teresa, Fischer, Krista, Forouhi, Nita G, Friedrich, Nele, Gjesing, Anette Marianne Prior, Glorioso, Nicola, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Gräßler, Jürgen, Grewal, Jagvir, Hamsten, Anders, Harder, Marie Neergaard, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew Tym, Havulinna, Aki S, Heliövaara, Markku, Hillege, Hans, Hofman, Albert, Holmen, Oddgeir, Homuth, Georg, Hottenga, Jouke-Jan, Hui, Jennie, Husemoen, Lise Lotte, Hysi, Pirro G, Isaacs, Aaron, Ittermann, Till, Jalilzadeh, Shapour, James, Alan L, Jørgensen, Torben, Jousilahti, Pekka, Jula, Antti, Marie Justesen, Johanne, Justice, Anne E, Kähönen, Mika, Karaleftheri, Maria, Tee Khaw, Kay, Keinanen-Kiukaanniemi, Sirkka M, Kinnunen, Leena, Knekt, Paul B, Koistinen, Heikki A, Kolcic, Ivana, Kooner, Ishminder K, Koskinen, Seppo, Kovacs, Peter, Kyriakou, Theodosios, Laitinen, Tomi, Langenberg, Claudia, Lewin, Alexandra M, Lichtner, Peter, Lindgren, Cecilia M, Lindström, Jaana, Linneberg, Allan, Lorbeer, Roberto, Lorentzon, Mattias, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Manunta, Paolo, Leach, Irene Mateo, McArdle, Wendy L, Mcknight, Barbara, Mohlke, Karen L, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Montasser, May E, Morris, Andrew P, Müller, Gabriele, Musk, Arthur W, Narisu, Narisu, Ong, Ken K, Oostra, Ben A, Osmond, Clive, Palotie, Aarno, Pankow, James S, Paternoster, Lavinia, Penninx, Brenda W, Pichler, Irene, Pilia, Maria G, Polašek, Ozren, Pramstaller, Peter P, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rayner, Nigel W, Ribel-Madsen, Rasmus, Rice, Treva K, Richards, Marcus, Ridker, Paul M, Rivadeneira, Fernando, Ryan, Kathy A, Sanna, Serena, Sarzynski, Mark A, Scholtens, Salome, Scott, Robert A, Sebert, Sylvain, Southam, Lorraine, Sparsø, Thomas Hempel, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stolk, Ronald P, Strauch, Konstantin, Stringham, Heather M, Swertz, Morris A, Swift, Amy J, Tönjes, Anke, Tsafantakis, Emmanouil, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vandenput, Liesbeth, Vartiainen, Erkki, Venturini, Cristina, Verweij, Niek, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Vonk, Judith M, Waeber, Gérard, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Winkler, Thomas W, Wright, Alan F, Yerges-Armstrong, Laura M, Hua Zhao, Jing, Carola Zillikens, M, Boomsma, Dorret I, Bouchard, Claude, Chambers, John C, Chasman, Daniel I, Cusi, Daniele, Gansevoort, Ron T, Gieger, Christian, Hansen, Torben, Hicks, Andrew A, Hu, Frank, Hveem, Kristian, Jarvelin, Marjo-Riitta, Kajantie, Eero, Kooner, Jaspal S, Kuh, Diana, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lehtimäki, Terho, Metspalu, Andres, Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J, Palmer, Lyle J, Pedersen, Oluf, Perola, Markus, Peters, Annette, Psaty, Bruce M, Puolijoki, Hannu, Rauramaa, Rainer, Rudan, Igor, Salomaa, Veikko, Schwarz, Peter E H, Shudiner, Alan R, Smit, Jan H, Sørensen, Thorkild I A, Spector, Timothy D, Stefansson, Kari, Stumvoll, Michael, Tremblay, Angelo, Tuomilehto, Jaakko, Uitterlinden, André G, Uusitupa, Matti, Völker, Uwe, Vollenweider, Peter, Wareham, Nicholas J, Watkins, Hugh, Wilson, James F, Zeggini, Eleftheria, Abecasis, Goncalo R, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, van Duijn, Cornelia M, Fox, Caroline, Groop, Leif C, Heid, Iris M, Hunter, David J, Kaplan, Robert C, McCarthy, Mark I, North, Kari E, O'Connell, Jeffrey R, Schlessinger, David, Thorsteinsdottir, Unnur, Strachan, David P, Frayling, Timothy, Hirschhorn, Joel N, Müller-Nurasyid, Martina, and Loos, Ruth J F

Abstract

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

Published
2016

4. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Ried, Janina S., primary, Jeff M., Janina, additional, Chu, Audrey Y., additional, Bragg-Gresham, Jennifer L., additional, van Dongen, Jenny, additional, Huffman, Jennifer E., additional, Ahluwalia, Tarunveer S., additional, Cadby, Gemma, additional, Eklund, Niina, additional, Eriksson, Joel, additional, Esko, Tõnu, additional, Feitosa, Mary F., additional, Goel, Anuj, additional, Gorski, Mathias, additional, Hayward, Caroline, additional, Heard-Costa, Nancy L., additional, Jackson, Anne U., additional, Jokinen, Eero, additional, Kanoni, Stavroula, additional, Kristiansson, Kati, additional, Kutalik, Zoltán, additional, Lahti, Jari, additional, Luan, Jian'an, additional, Mägi, Reedik, additional, Mahajan, Anubha, additional, Mangino, Massimo, additional, Medina-Gomez, Carolina, additional, Monda, Keri L., additional, Nolte, Ilja M., additional, Pérusse, Louis, additional, Prokopenko, Inga, additional, Qi, Lu, additional, Rose, Lynda M., additional, Salvi, Erika, additional, Smith, Megan T., additional, Snieder, Harold, additional, Stančáková, Alena, additional, Ju Sung, Yun, additional, Tachmazidou, Ioanna, additional, Teumer, Alexander, additional, Thorleifsson, Gudmar, additional, van der Harst, Pim, additional, Walker, Ryan W., additional, Wang, Sophie R., additional, Wild, Sarah H., additional, Willems, Sara M., additional, Wong, Andrew, additional, Zhang, Weihua, additional, Albrecht, Eva, additional, Couto Alves, Alexessander, additional, Bakker, Stephan J. L., additional, Barlassina, Cristina, additional, Bartz, Traci M., additional, Beilby, John, additional, Bellis, Claire, additional, Bergman, Richard N., additional, Bergmann, Sven, additional, Blangero, John, additional, Blüher, Matthias, additional, Boerwinkle, Eric, additional, Bonnycastle, Lori L., additional, Bornstein, Stefan R., additional, Bruinenberg, Marcel, additional, Campbell, Harry, additional, Chen, Yii-Der Ida, additional, Chiang, Charleston W. K., additional, Chines, Peter S., additional, Collins, Francis S, additional, Cucca, Fracensco, additional, Cupples, L Adrienne, additional, D’Avila, Francesca, additional, de Geus, Eco J .C., additional, Dedoussis, George, additional, Dimitriou, Maria, additional, Döring, Angela, additional, Eriksson, Johan G., additional, Farmaki, Aliki-Eleni, additional, Farrall, Martin, additional, Ferreira, Teresa, additional, Fischer, Krista, additional, Forouhi, Nita G., additional, Friedrich, Nele, additional, Gjesing, Anette Prior, additional, Glorioso, Nicola, additional, Graff, Mariaelisa, additional, Grallert, Harald, additional, Grarup, Niels, additional, Gräßler, Jürgen, additional, Grewal, Jagvir, additional, Hamsten, Anders, additional, Harder, Marie Neergaard, additional, Hartman, Catharina A., additional, Hassinen, Maija, additional, Hastie, Nicholas, additional, Hattersley, Andrew Tym, additional, Havulinna, Aki S., additional, Heliövaara, Markku, additional, Hillege, Hans, additional, Hofman, Albert, additional, Holmen, Oddgeir, additional, Homuth, Georg, additional, Hottenga, Jouke-Jan, additional, Hui, Jennie, additional, Husemoen, Lise Lotte, additional, Hysi, Pirro G., additional, Isaacs, Aaron, additional, Ittermann, Till, additional, Jalilzadeh, Shapour, additional, James, Alan L., additional, Jørgensen, Torben, additional, Jousilahti, Pekka, additional, Jula, Antti, additional, Marie Justesen, Johanne, additional, Justice, Anne E., additional, Kähönen, Mika, additional, Karaleftheri, Maria, additional, Tee Khaw, Kay, additional, Keinanen-Kiukaanniemi, Sirkka M., additional, Kinnunen, Leena, additional, Knekt, Paul B., additional, Koistinen, Heikki A., additional, Kolcic, Ivana, additional, Kooner, Ishminder K., additional, Koskinen, Seppo, additional, Kovacs, Peter, additional, Kyriakou, Theodosios, additional, Laitinen, Tomi, additional, Langenberg, Claudia, additional, Lewin, Alexandra M., additional, Lichtner, Peter, additional, Lindgren, Cecilia M., additional, Lindström, Jaana, additional, Linneberg, Allan, additional, Lorbeer, Roberto, additional, Lorentzon, Mattias, additional, Luben, Robert, additional, Lyssenko, Valeriya, additional, Männistö, Satu, additional, Manunta, Paolo, additional, Leach, Irene Mateo, additional, McArdle, Wendy L., additional, Mcknight, Barbara, additional, Mohlke, Karen L., additional, Mihailov, Evelin, additional, Milani, Lili, additional, Mills, Rebecca, additional, Montasser, May E., additional, Morris, Andrew P., additional, Müller, Gabriele, additional, Musk, Arthur W., additional, Narisu, Narisu, additional, Ong, Ken K., additional, Oostra, Ben A., additional, Osmond, Clive, additional, Palotie, Aarno, additional, Pankow, James S., additional, Paternoster, Lavinia, additional, Penninx, Brenda W., additional, Pichler, Irene, additional, Pilia, Maria G., additional, Polašek, Ozren, additional, Pramstaller, Peter P., additional, Raitakari, Olli T, additional, Rankinen, Tuomo, additional, Rao, D. C., additional, Rayner, Nigel W., additional, Ribel-Madsen, Rasmus, additional, Rice, Treva K., additional, Richards, Marcus, additional, Ridker, Paul M., additional, Rivadeneira, Fernando, additional, Ryan, Kathy A., additional, Sanna, Serena, additional, Sarzynski, Mark A., additional, Scholtens, Salome, additional, Scott, Robert A., additional, Sebert, Sylvain, additional, Southam, Lorraine, additional, Sparsø, Thomas Hempel, additional, Steinthorsdottir, Valgerdur, additional, Stirrups, Kathleen, additional, Stolk, Ronald P., additional, Strauch, Konstantin, additional, Stringham, Heather M., additional, Swertz, Morris A., additional, Swift, Amy J., additional, Tönjes, Anke, additional, Tsafantakis, Emmanouil, additional, van der Most, Peter J., additional, Van Vliet-Ostaptchouk, Jana V., additional, Vandenput, Liesbeth, additional, Vartiainen, Erkki, additional, Venturini, Cristina, additional, Verweij, Niek, additional, Viikari, Jorma S., additional, Vitart, Veronique, additional, Vohl, Marie-Claude, additional, Vonk, Judith M., additional, Waeber, Gérard, additional, Widén, Elisabeth, additional, Willemsen, Gonneke, additional, Wilsgaard, Tom, additional, Winkler, Thomas W., additional, Wright, Alan F., additional, Yerges-Armstrong, Laura M., additional, Hua Zhao, Jing, additional, Carola Zillikens, M., additional, Boomsma, Dorret I., additional, Bouchard, Claude, additional, Chambers, John C., additional, Chasman, Daniel I., additional, Cusi, Daniele, additional, Gansevoort, Ron T., additional, Gieger, Christian, additional, Hansen, Torben, additional, Hicks, Andrew A., additional, Hu, Frank, additional, Hveem, Kristian, additional, Jarvelin, Marjo-Riitta, additional, Kajantie, Eero, additional, Kooner, Jaspal S., additional, Kuh, Diana, additional, Kuusisto, Johanna, additional, Laakso, Markku, additional, Lakka, Timo A., additional, Lehtimäki, Terho, additional, Metspalu, Andres, additional, Njølstad, Inger, additional, Ohlsson, Claes, additional, Oldehinkel, Albertine J., additional, Palmer, Lyle J., additional, Pedersen, Oluf, additional, Perola, Markus, additional, Peters, Annette, additional, Psaty, Bruce M., additional, Puolijoki, Hannu, additional, Rauramaa, Rainer, additional, Rudan, Igor, additional, Salomaa, Veikko, additional, Schwarz, Peter E. H., additional, Shudiner, Alan R., additional, Smit, Jan H., additional, Sørensen, Thorkild I. A., additional, Spector, Timothy D., additional, Stefansson, Kari, additional, Stumvoll, Michael, additional, Tremblay, Angelo, additional, Tuomilehto, Jaakko, additional, Uitterlinden, André G., additional, Uusitupa, Matti, additional, Völker, Uwe, additional, Vollenweider, Peter, additional, Wareham, Nicholas J., additional, Watkins, Hugh, additional, Wilson, James F., additional, Zeggini, Eleftheria, additional, Abecasis, Goncalo R., additional, Boehnke, Michael, additional, Borecki, Ingrid B., additional, Deloukas, Panos, additional, van Duijn, Cornelia M., additional, Fox, Caroline, additional, Groop, Leif C., additional, Heid, Iris M., additional, Hunter, David J., additional, Kaplan, Robert C., additional, McCarthy, Mark I., additional, North, Kari E., additional, O'Connell, Jeffrey R., additional, Schlessinger, David, additional, Thorsteinsdottir, Unnur, additional, Strachan, David P., additional, Frayling, Timothy, additional, Hirschhorn, Joel N., additional, Müller-Nurasyid, Martina, additional, and Loos, Ruth J. F., additional

Published
2016
Full Text
View/download PDF

5. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Farmaki, Aliki-Eleni, Hui, Jennie, Gräßler, Jürgen, Van Der Most, Peter J., Walker, Ryan W., Cupples, L Adrienne, Holmen, Oddgeir, Hassinen, Maija, Pedersen, Oluf, Lichtner, Peter, Tachmazidou, Ioanna, Hillege, Hans, Tremblay, Angelo, Musk, Arthur W., Heard-Costa, Nancy L., Sørensen, Thorkild I. A., Völker, Uwe, Sebert, Sylvain, Eriksson, Joel, Bellis, Claire, Willemsen, Gonneke, Chen, Yii-Der Ida, Hofman, Albert, Pankow, James S., Huffman, Jennifer E., Boehnke, Michael, Jeff, Janina M., Qi, Lu, Thorsteinsdottir, Unnur, Hunter, David J., Ried, Janina S., Monda, Keri L., Hirschhorn, Joel N., Uusitupa, Matti, Grarup, Niels, Salvi, Erika, Mccarthy, Mark I., Laakso, Markku, Wright, Alan F., Feitosa, Mary F., Stefansson, Kari, Widén, Elisabeth, Friedrich, Nele, O'connell, Jeffrey R., Kyriakou, Theodosios, Lyssenko, Valeriya, Zeggini, Eleftheria, Teumer, Alexander, Justice, Anne E., Cadby, Gemma, Hu, Frank, Lindström, Jaana, Tee Khaw, Kay, Kovacs, Peter, Marie Justesen, Johanne, Mcardle, Wendy L., Willems, Sara M., Stringham, Heather M., Montasser, May E., Kuh, Diana, Isaacs, Aaron, Karaleftheri, Maria, Scott, Robert A., Rauramaa, Rainer, Jokinen, Eero, Schlessinger, David, Pilia, Maria G., North, Kari E., Ong, Ken K., Ittermann, Till, Lorbeer, Roberto, Couto Alves, Alexessander, Salomaa, Veikko, Luben, Robert, Hartman, Catharina A., Bouchard, Claude, Rayner, Nigel W., Hayward, Caroline, Rao, Ridker, Paul M., Peters, Annette, Hveem, Kristian, Vohl, Marie-Claude, Ribel-Madsen, Rasmus, Albrecht, Eva, Wilsgaard, Tom, Lorentzon, Mattias, Fox, Caroline, Palmer, Lyle J., Stolk, Ronald P., Carola Zillikens, Stirrups, Kathleen, Southam, Lorraine, Chasman, Daniel I., Forouhi, Nita G., Ryan, Kathy A., Esko, Toñu, Linneberg, Allan, Hastie, Nicholas, Wild, Sarah H., Palotie, Aarno, Mohlke, Karen L., Wareham, Nicholas J., Lakka, Timo A., Koistinen, Heikki A., Paternoster, Lavinia, Prokopenko, Inga, Osmond, Clive, Oostra, Ben A., Borecki, Ingrid B., Tuomilehto, Jaakko, Van Dongen, Jenny, Collins, Francis S, Grallert, Harald, Bragg-Gresham, Jennifer L., Smith, Megan T., Medina-Gomez, Carolina, Boerwinkle, Eric, Müller, Gabriele, Bornstein, Stefan R., Heliövaara, Markku, Jousilahti, Pekka, Kinnunen, Leena, Kooner, Jaspal S., Swift, Amy J., Kuusisto, Johanna, Loos, Ruth J. F., Zhao, Jing Hua, Ju Sung, Yun, Rankinen, Tuomo, Grewal, Jagvir, Bartz, Traci M., Hamsten, Anders, Döring, Angela, Hicks, Andrew A., Mägi, Reedik, Njølstad, Inger, Rudan, Igor, Rice, Treva K., Strachan, David P., De Geus, Eco J.C., Chiang, Charleston W. K., Watkins, Hugh, Kaplan, Robert C., Blüher, Matthias, Standáková, Alena, Luan, Jian'an, Cusi, Daniele, Homuth, Georg, Sarzynski, Mark A., Jarvelin, Marjo-Riitta, Ohlsson, Claes, Stumvoll, Michael, Groop, Leif C., Chambers, John C., Gjesing, Anette Prior, Penninx, Brenda W., Bruinenberg, Marcel, Strauch, Konstantin, Waeber, Gérard, Knekt, Paul B., Kolcic, Ivana, Husemoen, Lise Lotte, Dedoussis, George, Mahajan, Anubha, Fischer, Krista, Chu, Audrey Y., Lahti, Jari, Lehtimäki, Terho, Morris, Andrew P., Nolte, Ilja M., Havulinna, Aki S., Spector, Timothy D., Vitart, Veronique, Keinanen-Kiukaanniemi, Sirkka M., Gieger, Christian, Abecasis, Goncalo R., Metspalu, Andres, Sanna, Serena, Psaty, Bruce M., Goel, Anuj, Thorleifsson, Gudmar, Scholtens, Salome, Ferreira, Teresa, Viikari, Jorma S., Lewin, Alexandra M., Glorioso, Nicola, Mcknight, Barbara, Richards, Marcus, Winkler, Thomas W., Snieder, Harold, Männistö, Satu, Kähönen, Mika, Harder, Marie Neergaard, Laitinen, Tomi, Bergmann, Sven, Oldehinkel, Albertine J., Langenberg, Claudia, Wilson, James F., Pérusse, Louis, Kutalik, Zoltán, Dimitriou, Maria, Farrall, Martin, Zhang, Weihua, Tönjes, Anke, Wang, Sophie R., Verweij, Niek, Jackson, Anne U., Lindgren, Cecilia M., Bonnycastle, Lori L., Narisu, Narisu, Eklund, Niina, Müller-Nurasyid, Martina, Polašek, Ozren, Kooner, Ishminder K., Pichler, Irene, Pramstaller, Peter P., Smit, Jan H., Perola, Markus, Tsafantakis, Emmanouil, Beilby, John, Rivadeneira, Fernando, Sparsø, Thomas Hempel, Steinthorsdottir, Valgerdur, Graff, Mariaelisa, Manunta, Paolo, Wong, Andrew, Hottenga, Jouke-Jan, Raitakari, Olli T, Leach, Irene Mateo, Milani, Lili, Swertz, Morris A., Boomsma, Dorret I., Yerges-Armstrong, Laura M., James, Alan L., Ahluwalia, Tarunveer S., Vartiainen, Erkki, Blangero, John, Campbell, Harry, Uitterlinden, André G., Puolijoki, Hannu, Frayling, Timothy, Jula, Antti, Kristiansson, Kati, Eriksson, Johan G., Gansevoort, Ron T., Heid, Iris M., Kajantie, Eero, Bakker, Stephan J. L., Rose, Lynda M., Gorski, Mathias, Mangino, Massimo, Vollenweider, Peter, Van Der Harst, Pim, Van Duijn, Cornelia M., Koskinen, Seppo, Venturini, Cristina, Van Vliet-Ostaptchouk, Jana V., Mills, Rebecca, Jørgensen, Torben, Mihailov, Evelin, Vandenput, Liesbeth, Shudiner, Alan R., Barlassina, Cristina, Hattersley, Andrew Tym, Chines, Peter S., Hansen, Torben, D'avila, Francesca, Deloukas, Panos, Cucca, Fracensco, Vonk, Judith M., Hysi, Pirro G., Kanoni, Stavroula, Schwarz, Peter E. H., Jalilzadeh, Shapour, and Bergman, Richard N.

Subjects
2. Zero hunger
Abstract

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

6. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Ried, Janina S, Jeff M, Janina, Chu, Audrey Y, Bragg-Gresham, Jennifer L, Van Dongen, Jenny, Huffman, Jennifer E, Ahluwalia, Tarunveer S, Cadby, Gemma, Eklund, Niina, Eriksson, Joel, Esko, Tõnu, Feitosa, Mary F, Goel, Anuj, Gorski, Mathias, Hayward, Caroline, Heard-Costa, Nancy L, Jackson, Anne U, Jokinen, Eero, Kanoni, Stavroula, Kristiansson, Kati, Kutalik, Zoltán, Lahti, Jari, Luan, Jian'an, Mägi, Reedik, Mahajan, Anubha, Mangino, Massimo, Medina-Gomez, Carolina, Monda, Keri L, Nolte, Ilja M, Pérusse, Louis, Prokopenko, Inga, Qi, Lu, Rose, Lynda M, Salvi, Erika, Smith, Megan T, Snieder, Harold, Stančáková, Alena, Ju Sung, Yun, Tachmazidou, Ioanna, Teumer, Alexander, Thorleifsson, Gudmar, Van Der Harst, Pim, Walker, Ryan W, Wang, Sophie R, Wild, Sarah H, Willems, Sara M, Wong, Andrew, Zhang, Weihua, Albrecht, Eva, Couto Alves, Alexessander, Bakker, Stephan JL, Barlassina, Cristina, Bartz, Traci M, Beilby, John, Bellis, Claire, Bergman, Richard N, Bergmann, Sven, Blangero, John, Blüher, Matthias, Boerwinkle, Eric, Bonnycastle, Lori L, Bornstein, Stefan R, Bruinenberg, Marcel, Campbell, Harry, Chen, Yii-Der Ida, Chiang, Charleston WK, Chines, Peter S, Collins, Francis S, Cucca, Fracensco, Cupples, L Adrienne, D'Avila, Francesca, De Geus, Eco JC, Dedoussis, George, Dimitriou, Maria, Döring, Angela, Eriksson, Johan G, Farmaki, Aliki-Eleni, Farrall, Martin, Ferreira, Teresa, Fischer, Krista, Forouhi, Nita G, Friedrich, Nele, Gjesing, Anette Prior, Glorioso, Nicola, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Gräßler, Jürgen, Grewal, Jagvir, Hamsten, Anders, Harder, Marie Neergaard, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew Tym, Havulinna, Aki S, Heliövaara, Markku, Hillege, Hans, Hofman, Albert, Holmen, Oddgeir, Homuth, Georg, Hottenga, Jouke-Jan, Hui, Jennie, Husemoen, Lise Lotte, Hysi, Pirro G, Isaacs, Aaron, Ittermann, Till, Jalilzadeh, Shapour, James, Alan L, Jørgensen, Torben, Jousilahti, Pekka, Jula, Antti, Marie Justesen, Johanne, Justice, Anne E, Kähönen, Mika, Karaleftheri, Maria, Tee Khaw, Kay, Keinanen-Kiukaanniemi, Sirkka M, Kinnunen, Leena, Knekt, Paul B, Koistinen, Heikki A, Kolcic, Ivana, Kooner, Ishminder K, Koskinen, Seppo, Kovacs, Peter, Kyriakou, Theodosios, Laitinen, Tomi, Langenberg, Claudia, Lewin, Alexandra M, Lichtner, Peter, Lindgren, Cecilia M, Lindström, Jaana, Linneberg, Allan, Lorbeer, Roberto, Lorentzon, Mattias, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Manunta, Paolo, Leach, Irene Mateo, McArdle, Wendy L, Mcknight, Barbara, Mohlke, Karen L, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Montasser, May E, Morris, Andrew P, Müller, Gabriele, Musk, Arthur W, Narisu, Narisu, Ong, Ken K, Oostra, Ben A, Osmond, Clive, Palotie, Aarno, Pankow, James S, Paternoster, Lavinia, Penninx, Brenda W, Pichler, Irene, Pilia, Maria G, Polašek, Ozren, Pramstaller, Peter P, Raitakari, Olli T, Rankinen, Tuomo, Rao, DC, Rayner, Nigel W, Ribel-Madsen, Rasmus, Rice, Treva K, Richards, Marcus, Ridker, Paul M, Rivadeneira, Fernando, Ryan, Kathy A, Sanna, Serena, Sarzynski, Mark A, Scholtens, Salome, Scott, Robert A, Sebert, Sylvain, Southam, Lorraine, Sparsø, Thomas Hempel, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stolk, Ronald P, Strauch, Konstantin, Stringham, Heather M, Swertz, Morris A, Swift, Amy J, Tönjes, Anke, Tsafantakis, Emmanouil, Van Der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vandenput, Liesbeth, Vartiainen, Erkki, Venturini, Cristina, Verweij, Niek, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Vonk, Judith M, Waeber, Gérard, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Winkler, Thomas W, Wright, Alan F, Yerges-Armstrong, Laura M, Hua Zhao, Jing, Zillikens, M Carola, Boomsma, Dorret I, Bouchard, Claude, Chambers, John C, Chasman, Daniel I, Cusi, Daniele, Gansevoort, Ron T, Gieger, Christian, Hansen, Torben, Hicks, Andrew A, Hu, Frank, Hveem, Kristian, Jarvelin, Marjo-Riitta, Kajantie, Eero, Kooner, Jaspal S, Kuh, Diana, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lehtimäki, Terho, Metspalu, Andres, Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J, Palmer, Lyle J, Pedersen, Oluf, Perola, Markus, Peters, Annette, Psaty, Bruce M, Puolijoki, Hannu, Rauramaa, Rainer, Rudan, Igor, Salomaa, Veikko, Schwarz, Peter EH, Shudiner, Alan R, Smit, Jan H, Sørensen, Thorkild IA, Spector, Timothy D, Stefansson, Kari, Stumvoll, Michael, Tremblay, Angelo, Tuomilehto, Jaakko, Uitterlinden, André G, Uusitupa, Matti, Völker, Uwe, Vollenweider, Peter, Wareham, Nicholas J, Watkins, Hugh, Wilson, James F, Zeggini, Eleftheria, Abecasis, Goncalo R, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Van Duijn, Cornelia M, Fox, Caroline, Groop, Leif C, Heid, Iris M, Hunter, David J, Kaplan, Robert C, McCarthy, Mark I, North, Kari E, O'Connell, Jeffrey R, Schlessinger, David, Thorsteinsdottir, Unnur, Strachan, David P, Frayling, Timothy, Hirschhorn, Joel N, Müller-Nurasyid, Martina, and Loos, Ruth JF

Subjects
2. Zero hunger, Principal Component Analysis, Anthropometry, Genotype, Models, Genetic, Body Size, Humans, Genome-Wide Association Study
Abstract

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

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