A Principal Component Meta-Analysis on Multiple Anthropometric Traits Identifies Novel Loci for Body Shape

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; Magi, 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; Ju Sung, Yun; Tachmazidou, Ioanna; Teumer, Alexander; Thorleifsson, Gudmar; van der Harst, Pim; Walker, Ryan W.; Wang, Sophie R.; Wild, Sarah H.; Willems, Sarah 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; Bluher, 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, Francesco; Cupples, L. Adrienne; D'Avila, Francesca; de Geus, Eco J. C.; Dedoussis, George; Dimitriou, Maria; Doring, 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; Grassler, Jurgen; 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 J.; Ittermann, Till; Jalilzadeh, Shapour; James, Alan L.; Jorgensen, Torben; Jousilahti, Pekka; Jula, Antti; Marie Justesen, Johanne; Justice, Anne E.; Kahonen, 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.; 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.; Muller, 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, Dabeeru 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 E.; Stolk, Ronald P.; Strauch, Konstantin; Stringham, Heather M.; Swertz, Morris A.; Swift, Amy J.; Tonjes, 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.; 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.; Lehtimaki, 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; Volker, 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.; Muller-Nurasyid, Martina; & Loos, Ruth J. F. (2016). A Principal Component Meta-Analysis on Multiple Anthropometric Traits Identifies Novel Loci for Body Shape. Nature Communications, 7, 13357. PMCID: PMC5114527

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; Magi, 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; Ju Sung, Yun; Tachmazidou, Ioanna; Teumer, Alexander; Thorleifsson, Gudmar; van der Harst, Pim; Walker, Ryan W.; Wang, Sophie R.; Wild, Sarah H.; Willems, Sarah 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; Bluher, 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, Francesco; Cupples, L. Adrienne; D'Avila, Francesca; de Geus, Eco J. C.; Dedoussis, George; Dimitriou, Maria; Doring, 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; Grassler, Jurgen; 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 J.; Ittermann, Till; Jalilzadeh, Shapour; James, Alan L.; Jorgensen, Torben; Jousilahti, Pekka; Jula, Antti; Marie Justesen, Johanne; Justice, Anne E.; Kahonen, 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.; 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.; Muller, 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, Dabeeru 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 E.; Stolk, Ronald P.; Strauch, Konstantin; Stringham, Heather M.; Swertz, Morris A.; Swift, Amy J.; Tonjes, 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.; 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.; Lehtimaki, 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; Volker, 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.; Muller-Nurasyid, Martina; & Loos, Ruth J. F. (2016). A Principal Component Meta-Analysis on Multiple Anthropometric Traits Identifies Novel Loci for Body Shape. Nature Communications, 7, 13357. PMCID: PMC5114527

Octet Stream icon 9717.ris — Octet Stream, 7 kB (7801 bytes)

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.




JOUR



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
Magi, 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
Ju Sung, Yun
Tachmazidou, Ioanna
Teumer, Alexander
Thorleifsson, Gudmar
van der Harst, Pim
Walker, Ryan W.
Wang, Sophie R.
Wild, Sarah H.
Willems, Sarah 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
Bluher, 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, Francesco
Cupples, L. Adrienne
D'Avila, Francesca
de Geus, Eco J. C.
Dedoussis, George
Dimitriou, Maria
Doring, 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
Grassler, Jurgen
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 J.
Ittermann, Till
Jalilzadeh, Shapour
James, Alan L.
Jorgensen, Torben
Jousilahti, Pekka
Jula, Antti
Marie Justesen, Johanne
Justice, Anne E.
Kahonen, 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.
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.
Muller, 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, Dabeeru 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 E.
Stolk, Ronald P.
Strauch, Konstantin
Stringham, Heather M.
Swertz, Morris A.
Swift, Amy J.
Tonjes, 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.
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.
Lehtimaki, 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
Volker, 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.
Muller-Nurasyid, Martina
Loos, Ruth J. F.



2016


Nature Communications

7


13357








PMC5114527


9717

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