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

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

doi:10.1038/ncomms13357

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

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

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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.

Original language	English
Article number	13357
Journal	Nature Communications
Volume	7
Number of pages	11
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms13357
Publication status	Published - 23 Nov 2016

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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shapeFinal published version, 836 KBLicence: CC BY

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Ried, J. S., Jeff M, J., Chu, A. Y., Bragg-Gresham, J. L., van Dongen, J., Huffman, J. E., Ahluwalia, T. V. S., Cadby, G., Eklund, N., Eriksson, J., Esko, T., Feitosa, M. F., Goel, A., Gorski, M., Hayward, C., Heard-Costa, N. L., Jackson, A. U., Jokinen, E., Kanoni, S., ... Loos, R. J. F. (2016). A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape. Nature Communications, 7, [13357]. https://doi.org/10.1038/ncomms13357

Ried, JS, Jeff M, J, Chu, AY, Bragg-Gresham, JL, van Dongen, J, Huffman, JE, Ahluwalia, TVS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, J, Mägi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM, Pérusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, MT, Snieder, H, Stančáková, A, Ju Sung, Y, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, SM, Wong, A, Zhang, W, Albrecht, E, Couto Alves, A, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Blüher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, Y-DI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Döring, A, Eriksson, JG, Farmaki, A-E, Farrall, M, Ferreira, T, Fischer, K, Forouhi, NG, Friedrich, N, Gjesing, AMP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Gräßler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliövaara, M, Hillege, H, Hofman, A, Holmen, O, Homuth, G, Hottenga, J-J, Hui, J, Husemoen, LL, Hysi, PG, Isaacs, A, Ittermann, T, Jalilzadeh, S, James, AL, Jørgensen, T, Jousilahti, P, Jula, A, Marie Justesen, J, Justice, AE, Kähönen, M, Karaleftheri, M, Tee Khaw, K, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindström, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Männistö, S, Manunta, P, Leach, IM, McArdle, WL, Mcknight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Müller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, BA, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polašek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, F, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, S, Scott, RA, Sebert, S, Southam, L, Sparsø, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP, Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tönjes, A, Tsafantakis, E, van der Most, PJ, Van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N, Viikari, JS, Vitart, V, Vohl, M-C, Vonk, JM, Waeber, G, Widén, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Hua Zhao, J, Carola Zillikens, M, Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, M-R, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimäki, T, Metspalu, A, Njølstad, I, Ohlsson, C, Oldehinkel, AJ, Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, AR, Smit, JH, Sørensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, AG, Uusitupa, M, Völker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, van Duijn, CM, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Müller-Nurasyid, M & Loos, RJF 2016, 'A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape', Nature Communications, vol. 7, 13357. https://doi.org/10.1038/ncomms13357

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title = "A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape",

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.",

author = "Ried, {Janina S} and {Jeff M}, Janina and Chu, {Audrey Y} and Bragg-Gresham, {Jennifer L} and {van Dongen}, Jenny and Huffman, {Jennifer E} and Ahluwalia, {Tarun Veer Singh} and Gemma Cadby and Niina Eklund and Joel Eriksson and T{\~o}nu Esko and Feitosa, {Mary F} and Anuj Goel and Mathias Gorski and Caroline Hayward and Heard-Costa, {Nancy L} and Jackson, {Anne U} and Eero Jokinen and Stavroula Kanoni and Kati Kristiansson and Zolt{\'a}n Kutalik and Jari Lahti and Jian'an Luan and Reedik M{\"a}gi and Anubha Mahajan and Massimo Mangino and Carolina Medina-Gomez and Monda, {Keri L} and Nolte, {Ilja M} and Louis P{\'e}russe and Inga Prokopenko and Lu Qi and Rose, {Lynda M} and Erika Salvi and Smith, {Megan T} and Harold Snieder and Alena Stan{\v c}{\'a}kov{\'a} and {Ju Sung}, Yun and Ioanna Tachmazidou and Alexander Teumer and Gudmar Thorleifsson and {van der Harst}, Pim and Walker, {Ryan W} and Wang, {Sophie R} and Wild, {Sarah H} and Willems, {Sara M} and Andrew Wong and Weihua Zhang and Eva Albrecht and {Couto Alves}, Alexessander and Bakker, {Stephan J L} and Cristina Barlassina and Bartz, {Traci M} and John Beilby and Claire Bellis and Bergman, {Richard N} and Sven Bergmann and John Blangero and Matthias Bl{\"u}her and Eric Boerwinkle and Bonnycastle, {Lori L} and Bornstein, {Stefan R} and Marcel Bruinenberg and Harry Campbell and Chen, {Yii-Der Ida} and Chiang, {Charleston W K} and Chines, {Peter S} and Collins, {Francis S} and Fracensco Cucca and Cupples, {L Adrienne} and Francesca D'Avila and {de Geus}, {Eco J C} and George Dedoussis and Maria Dimitriou and Angela D{\"o}ring and Eriksson, {Johan G} and Aliki-Eleni Farmaki and Martin Farrall and Teresa Ferreira and Krista Fischer and Forouhi, {Nita G} and Nele Friedrich and Gjesing, {Anette Marianne Prior} and Nicola Glorioso and Mariaelisa Graff and Harald Grallert and Niels Grarup and J{\"u}rgen Gr{\"a}{\ss}ler and Jagvir Grewal and Anders Hamsten and Harder, {Marie Neergaard} and Hartman, {Catharina A} and Maija Hassinen and Nicholas Hastie and Hattersley, {Andrew Tym} and Havulinna, {Aki S} and Markku Heli{\"o}vaara and Hans Hillege and Albert Hofman and Oddgeir Holmen and Georg Homuth and Jouke-Jan Hottenga and Jennie Hui and Husemoen, {Lise Lotte} and Hysi, {Pirro G} and Aaron Isaacs and Till Ittermann and Shapour Jalilzadeh and James, {Alan L} and Torben J{\o}rgensen and Pekka Jousilahti and Antti Jula and {Marie Justesen}, Johanne and Justice, {Anne E} and Mika K{\"a}h{\"o}nen and Maria Karaleftheri and {Tee Khaw}, Kay and Keinanen-Kiukaanniemi, {Sirkka M} and Leena Kinnunen and Knekt, {Paul B} and Koistinen, {Heikki A} and Ivana Kolcic and Kooner, {Ishminder K} and Seppo Koskinen and Peter Kovacs and Theodosios Kyriakou and Tomi Laitinen and Claudia Langenberg and Lewin, {Alexandra M} and Peter Lichtner and Lindgren, {Cecilia M} and Jaana Lindstr{\"o}m and Allan Linneberg and Roberto Lorbeer and Mattias Lorentzon and Robert Luben and Valeriya Lyssenko and Satu M{\"a}nnist{\"o} and Paolo Manunta and Leach, {Irene Mateo} and McArdle, {Wendy L} and Barbara Mcknight and Mohlke, {Karen L} and Evelin Mihailov and Lili Milani and Rebecca Mills and Montasser, {May E} and Morris, {Andrew P} and Gabriele M{\"u}ller and Musk, {Arthur W} and Narisu Narisu and Ong, {Ken K} and Oostra, {Ben A} and Clive Osmond and Aarno Palotie and Pankow, {James S} and Lavinia Paternoster and Penninx, {Brenda W} and Irene Pichler and Pilia, {Maria G} and Ozren Pola{\v s}ek and Pramstaller, {Peter P} and Raitakari, {Olli T} and Tuomo Rankinen and Rao, {D C} and Rayner, {Nigel W} and Rasmus Ribel-Madsen and Rice, {Treva K} and Marcus Richards and Ridker, {Paul M} and Fernando Rivadeneira and Ryan, {Kathy A} and Serena Sanna and Sarzynski, {Mark A} and Salome Scholtens and Scott, {Robert A} and Sylvain Sebert and Lorraine Southam and Spars{\o}, {Thomas Hempel} and Valgerdur Steinthorsdottir and Kathleen Stirrups and Stolk, {Ronald P} and Konstantin Strauch and Stringham, {Heather M} and Swertz, {Morris A} and Swift, {Amy J} and Anke T{\"o}njes and Emmanouil Tsafantakis and {van der Most}, {Peter J} and {Van Vliet-Ostaptchouk}, {Jana V} and Liesbeth Vandenput and Erkki Vartiainen and Cristina Venturini and Niek Verweij and Viikari, {Jorma S} and Veronique Vitart and Marie-Claude Vohl and Vonk, {Judith M} and G{\'e}rard Waeber and Elisabeth Wid{\'e}n and Gonneke Willemsen and Tom Wilsgaard and Winkler, {Thomas W} and Wright, {Alan F} and Yerges-Armstrong, {Laura M} and {Hua Zhao}, Jing and {Carola Zillikens}, M and Boomsma, {Dorret I} and Claude Bouchard and Chambers, {John C} and Chasman, {Daniel I} and Daniele Cusi and Gansevoort, {Ron T} and Christian Gieger and Torben Hansen and Hicks, {Andrew A} and Frank Hu and Kristian Hveem and Marjo-Riitta Jarvelin and Eero Kajantie and Kooner, {Jaspal S} and Diana Kuh and Johanna Kuusisto and Markku Laakso and Lakka, {Timo A} and Terho Lehtim{\"a}ki and Andres Metspalu and Inger Nj{\o}lstad and Claes Ohlsson and Oldehinkel, {Albertine J} and Palmer, {Lyle J} and Oluf Pedersen and Markus Perola and Annette Peters and Psaty, {Bruce M} and Hannu Puolijoki and Rainer Rauramaa and Igor Rudan and Veikko Salomaa and Schwarz, {Peter E H} and Shudiner, {Alan R} and Smit, {Jan H} and S{\o}rensen, {Thorkild I A} and Spector, {Timothy D} and Kari Stefansson and Michael Stumvoll and Angelo Tremblay and Jaakko Tuomilehto and Uitterlinden, {Andr{\'e} G} and Matti Uusitupa and Uwe V{\"o}lker and Peter Vollenweider and Wareham, {Nicholas J} and Hugh Watkins and Wilson, {James F} and Eleftheria Zeggini and Abecasis, {Goncalo R} and Michael Boehnke and Borecki, {Ingrid B} and Panos Deloukas and {van Duijn}, {Cornelia M} and Caroline Fox and Groop, {Leif C} and Heid, {Iris M} and Hunter, {David J} and Kaplan, {Robert C} and McCarthy, {Mark I} and North, {Kari E} and O'Connell, {Jeffrey R} and David Schlessinger and Unnur Thorsteinsdottir and Strachan, {David P} and Timothy Frayling and Hirschhorn, {Joel N} 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doi = "10.1038/ncomms13357",

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}

TY - JOUR

T1 - A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

AU - Ried, Janina S

AU - Jeff M, Janina

AU - Chu, Audrey Y

AU - Bragg-Gresham, Jennifer L

AU - van Dongen, Jenny

AU - Huffman, Jennifer E

AU - Ahluwalia, Tarun Veer Singh

AU - Cadby, Gemma

AU - Eklund, Niina

AU - Eriksson, Joel

AU - Esko, Tõnu

AU - Feitosa, Mary F

AU - Goel, Anuj

AU - Gorski, Mathias

AU - Hayward, Caroline

AU - Heard-Costa, Nancy L

AU - Jackson, Anne U

AU - Jokinen, Eero

AU - Kanoni, Stavroula

AU - Kristiansson, Kati

AU - Kutalik, Zoltán

AU - Lahti, Jari

AU - Luan, Jian'an

AU - Mägi, Reedik

AU - Mahajan, Anubha

AU - Mangino, Massimo

AU - Medina-Gomez, Carolina

AU - Monda, Keri L

AU - Nolte, Ilja M

AU - Pérusse, Louis

AU - Prokopenko, Inga

AU - Qi, Lu

AU - Rose, Lynda M

AU - Salvi, Erika

AU - Smith, Megan T

AU - Snieder, Harold

AU - Stančáková, Alena

AU - Ju Sung, Yun

AU - Tachmazidou, Ioanna

AU - Teumer, Alexander

AU - Thorleifsson, Gudmar

AU - van der Harst, Pim

AU - Walker, Ryan W

AU - Wang, Sophie R

AU - Wild, Sarah H

AU - Willems, Sara M

AU - Wong, Andrew

AU - Zhang, Weihua

AU - Albrecht, Eva

AU - Couto Alves, Alexessander

AU - Bakker, Stephan J L

AU - Barlassina, Cristina

AU - Bartz, Traci M

AU - Beilby, John

AU - Bellis, Claire

AU - Bergman, Richard N

AU - Bergmann, Sven

AU - Blangero, John

AU - Blüher, Matthias

AU - Boerwinkle, Eric

AU - Bonnycastle, Lori L

AU - Bornstein, Stefan R

AU - Bruinenberg, Marcel

AU - Campbell, Harry

AU - Chen, Yii-Der Ida

AU - Chiang, Charleston W K

AU - Chines, Peter S

AU - Collins, Francis S

AU - Cucca, Fracensco

AU - Cupples, L Adrienne

AU - D'Avila, Francesca

AU - de Geus, Eco J C

AU - Dedoussis, George

AU - Dimitriou, Maria

AU - Döring, Angela

AU - Eriksson, Johan G

AU - Farmaki, Aliki-Eleni

AU - Farrall, Martin

AU - Ferreira, Teresa

AU - Fischer, Krista

AU - Forouhi, Nita G

AU - Friedrich, Nele

AU - Gjesing, Anette Marianne Prior

AU - Glorioso, Nicola

AU - Graff, Mariaelisa

AU - Grallert, Harald

AU - Grarup, Niels

AU - Gräßler, Jürgen

AU - Grewal, Jagvir

AU - Hamsten, Anders

AU - Harder, Marie Neergaard

AU - Hartman, Catharina A

AU - Hassinen, Maija

AU - Hastie, Nicholas

AU - Hattersley, Andrew Tym

AU - Havulinna, Aki S

AU - Heliövaara, Markku

AU - Hillege, Hans

AU - Hofman, Albert

AU - Holmen, Oddgeir

AU - Homuth, Georg

AU - Hottenga, Jouke-Jan

AU - Hui, Jennie

AU - Husemoen, Lise Lotte

AU - Hysi, Pirro G

AU - Isaacs, Aaron

AU - Ittermann, Till

AU - Jalilzadeh, Shapour

AU - James, Alan L

AU - Jørgensen, Torben

AU - Jousilahti, Pekka

AU - Jula, Antti

AU - Marie Justesen, Johanne

AU - Justice, Anne E

AU - Kähönen, Mika

AU - Karaleftheri, Maria

AU - Tee Khaw, Kay

AU - Keinanen-Kiukaanniemi, Sirkka M

AU - Kinnunen, Leena

AU - Knekt, Paul B

AU - Koistinen, Heikki A

AU - Kolcic, Ivana

AU - Kooner, Ishminder K

AU - Koskinen, Seppo

AU - Kovacs, Peter

AU - Kyriakou, Theodosios

AU - Laitinen, Tomi

AU - Langenberg, Claudia

AU - Lewin, Alexandra M

AU - Lichtner, Peter

AU - Lindgren, Cecilia M

AU - Lindström, Jaana

AU - Linneberg, Allan

AU - Lorbeer, Roberto

AU - Lorentzon, Mattias

AU - Luben, Robert

AU - Lyssenko, Valeriya

AU - Männistö, Satu

AU - Manunta, Paolo

AU - Leach, Irene Mateo

AU - McArdle, Wendy L

AU - Mcknight, Barbara

AU - Mohlke, Karen L

AU - Mihailov, Evelin

AU - Milani, Lili

AU - Mills, Rebecca

AU - Montasser, May E

AU - Morris, Andrew P

AU - Müller, Gabriele

AU - Musk, Arthur W

AU - Narisu, Narisu

AU - Ong, Ken K

AU - Oostra, Ben A

AU - Osmond, Clive

AU - Palotie, Aarno

AU - Pankow, James S

AU - Paternoster, Lavinia

AU - Penninx, Brenda W

AU - Pichler, Irene

AU - Pilia, Maria G

AU - Polašek, Ozren

AU - Pramstaller, Peter P

AU - Raitakari, Olli T

AU - Rankinen, Tuomo

AU - Rao, D C

AU - Rayner, Nigel W

AU - Ribel-Madsen, Rasmus

AU - Rice, Treva K

AU - Richards, Marcus

AU - Ridker, Paul M

AU - Rivadeneira, Fernando

AU - Ryan, Kathy A

AU - Sanna, Serena

AU - Sarzynski, Mark A

AU - Scholtens, Salome

AU - Scott, Robert A

AU - Sebert, Sylvain

AU - Southam, Lorraine

AU - Sparsø, Thomas Hempel

AU - Steinthorsdottir, Valgerdur

AU - Stirrups, Kathleen

AU - Stolk, Ronald P

AU - Strauch, Konstantin

AU - Stringham, Heather M

AU - Swertz, Morris A

AU - Swift, Amy J

AU - Tönjes, Anke

AU - Tsafantakis, Emmanouil

AU - van der Most, Peter J

AU - Van Vliet-Ostaptchouk, Jana V

AU - Vandenput, Liesbeth

AU - Vartiainen, Erkki

AU - Venturini, Cristina

AU - Verweij, Niek

AU - Viikari, Jorma S

AU - Vitart, Veronique

AU - Vohl, Marie-Claude

AU - Vonk, Judith M

AU - Waeber, Gérard

AU - Widén, Elisabeth

AU - Willemsen, Gonneke

AU - Wilsgaard, Tom

AU - Winkler, Thomas W

AU - Wright, Alan F

AU - Yerges-Armstrong, Laura M

AU - Hua Zhao, Jing

AU - Carola Zillikens, M

AU - Boomsma, Dorret I

AU - Bouchard, Claude

AU - Chambers, John C

AU - Chasman, Daniel I

AU - Cusi, Daniele

AU - Gansevoort, Ron T

AU - Gieger, Christian

AU - Hansen, Torben

AU - Hicks, Andrew A

AU - Hu, Frank

AU - Hveem, Kristian

AU - Jarvelin, Marjo-Riitta

AU - Kajantie, Eero

AU - Kooner, Jaspal S

AU - Kuh, Diana

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Lakka, Timo A

AU - Lehtimäki, Terho

AU - Metspalu, Andres

AU - Njølstad, Inger

AU - Ohlsson, Claes

AU - Oldehinkel, Albertine J

AU - Palmer, Lyle J

AU - Pedersen, Oluf

AU - Perola, Markus

AU - Peters, Annette

AU - Psaty, Bruce M

AU - Puolijoki, Hannu

AU - Rauramaa, Rainer

AU - Rudan, Igor

AU - Salomaa, Veikko

AU - Schwarz, Peter E H

AU - Shudiner, Alan R

AU - Smit, Jan H

AU - Sørensen, Thorkild I A

AU - Spector, Timothy D

AU - Stefansson, Kari

AU - Stumvoll, Michael

AU - Tremblay, Angelo

AU - Tuomilehto, Jaakko

AU - Uitterlinden, André G

AU - Uusitupa, Matti

AU - Völker, Uwe

AU - Vollenweider, Peter

AU - Wareham, Nicholas J

AU - Watkins, Hugh

AU - Wilson, James F

AU - Zeggini, Eleftheria

AU - Abecasis, Goncalo R

AU - Boehnke, Michael

AU - Borecki, Ingrid B

AU - Deloukas, Panos

AU - van Duijn, Cornelia M

AU - Fox, Caroline

AU - Groop, Leif C

AU - Heid, Iris M

AU - Hunter, David J

AU - Kaplan, Robert C

AU - McCarthy, Mark I

AU - North, Kari E

AU - O'Connell, Jeffrey R

AU - Schlessinger, David

AU - Thorsteinsdottir, Unnur

AU - Strachan, David P

AU - Frayling, Timothy

AU - Hirschhorn, Joel N

AU - Müller-Nurasyid, Martina

AU - Loos, Ruth J F

PY - 2016/11/23

Y1 - 2016/11/23

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms13357

DO - 10.1038/ncomms13357

M3 - Journal article

C2 - 27876822

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 13357

ER -

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

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