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 | |
Publication status | Published - 23 Nov 2016 |
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- 10.1038/ncomms13357Licence: CC BY
- 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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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape. / 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.
In: Nature Communications, Vol. 7, 13357, 23.11.2016.Research output: Contribution to journal › Journal article › Research › peer-review
}
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
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 13357
ER -