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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 and Eriksson, Joel , et al. (2016) In Nature Communications 7.
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... (More)

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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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
7
article number
13357
publisher
Nature Publishing Group
external identifiers
  • scopus:85000900079
  • pmid:27876822
  • wos:000388319700001
ISSN
2041-1723
DOI
10.1038/ncomms13357
language
English
LU publication?
yes
id
07f751f5-3bc7-4e81-a03e-c72b40a4600c
date added to LUP
2017-01-02 10:24:10
date last changed
2024-03-07 19:41:33
@article{07f751f5-3bc7-4e81-a03e-c72b40a4600c,
  abstract     = {{<p>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 &gt;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.</p>}},
  author       = {{Ried, Janina S. and Jeff, Janina M. and Chu, Audrey Y. and Bragg-Gresham, Jennifer L. and Van Dongen, Jenny and Huffman, Jennifer E. and Ahluwalia, Tarunveer S. and Cadby, Gemma and Eklund, Niina and Eriksson, Joel and Esko, Toñu and Feitosa, Mary F. and Goel, Anuj and Gorski, Mathias and Hayward, Caroline and Heard-Costa, Nancy L. and Jackson, Anne U. and Jokinen, Eero and Kanoni, Stavroula and Kristiansson, Kati and Kutalik, Zoltán and Lahti, Jari and Luan, Jian'an and Mägi, Reedik and Mahajan, Anubha and Mangino, Massimo and Medina-Gomez, Carolina and Monda, Keri L. and Nolte, Ilja M. and Pérusse, Louis and Prokopenko, Inga and Qi, Lu and Rose, Lynda M. and Salvi, Erika and Smith, Megan T. and Snieder, Harold and Standáková, Alena and Ju Sung, Yun and Tachmazidou, Ioanna and Teumer, Alexander and Thorleifsson, Gudmar and Van Der Harst, Pim and Walker, Ryan W. and Wang, Sophie R. and Wild, Sarah H. and Willems, Sara M. and Wong, Andrew and Zhang, Weihua and Albrecht, Eva and Couto Alves, Alexessander and Bakker, Stephan J L and Barlassina, Cristina and Bartz, Traci M. and Beilby, John and Bellis, Claire and Bergman, Richard N. and Bergmann, Sven and Blangero, John and Blüher, Matthias and Boerwinkle, Eric and Bonnycastle, Lori L. and Bornstein, Stefan R. and Bruinenberg, Marcel and Campbell, Harry and Chen, Yii Der Ida and Chiang, Charleston W K and Chines, Peter S. and Collins, Francis S. and Cucca, Fracensco and Cupples, L. Adrienne and D'avila, Francesca and De Geus, Eco J C and Dedoussis, George and Dimitriou, Maria and Döring, Angela and Eriksson, Johan G. and Farmaki, Aliki Eleni and Farrall, Martin and Ferreira, Teresa and Fischer, Krista and Forouhi, Nita G. and Friedrich, Nele and Gjesing, Anette Prior and Glorioso, Nicola and Graff, Mariaelisa and Grallert, Harald and Grarup, Niels and Gräßler, Jürgen and Grewal, Jagvir and Hamsten, Anders and Harder, Marie Neergaard and Hartman, Catharina A. and Hassinen, Maija and Hastie, Nicholas and Hattersley, Andrew Tym and Havulinna, Aki S. and Heliövaara, Markku and Hillege, Hans and Hofman, Albert and Holmen, Oddgeir and Homuth, Georg and Hottenga, Jouke Jan and Hui, Jennie and Husemoen, Lise Lotte and Hysi, Pirro G. and Isaacs, Aaron and Ittermann, Till and Jalilzadeh, Shapour and James, Alan L. and Jørgensen, Torben and Jousilahti, Pekka and Jula, Antti and Marie Justesen, Johanne and Justice, Anne E. and Kähönen, Mika and Karaleftheri, Maria and Tee Khaw, Kay and Keinanen-Kiukaanniemi, Sirkka M. and Kinnunen, Leena and Knekt, Paul B. and Koistinen, Heikki A. and Kolcic, Ivana and Kooner, Ishminder K. and Koskinen, Seppo and Kovacs, Peter and Kyriakou, Theodosios and Laitinen, Tomi and Langenberg, Claudia and Lewin, Alexandra M. and Lichtner, Peter and Lindgren, Cecilia M. and Lindström, Jaana and Linneberg, Allan and Lorbeer, Roberto and Lorentzon, Mattias and Luben, Robert and Lyssenko, Valeriya and Männistö, Satu and Manunta, Paolo and Leach, Irene Mateo and Mcardle, Wendy L. and Mcknight, Barbara and Mohlke, Karen L. and Mihailov, Evelin and Milani, Lili and Mills, Rebecca and Montasser, May E. and Morris, Andrew P. and Müller, Gabriele and Musk, Arthur W. and Narisu, Narisu and Ong, Ken K. and Oostra, Ben A. and Osmond, Clive and Palotie, Aarno and Pankow, James S. and Paternoster, Lavinia and Penninx, Brenda W. and Pichler, Irene and Pilia, Maria G. and Polašek, Ozren and Pramstaller, Peter P. and Raitakari, Olli T. and Rankinen, Tuomo and Rao, D. C. and Rayner, Nigel W. and Ribel-Madsen, Rasmus and Rice, Treva K. and Richards, Marcus and Ridker, Paul M. and Rivadeneira, Fernando and Ryan, Kathy A. and Sanna, Serena and Sarzynski, Mark A. and Scholtens, Salome and Scott, Robert A. and Sebert, Sylvain and Southam, Lorraine and Sparsø, Thomas Hempel and Steinthorsdottir, Valgerdur and Stirrups, Kathleen and Stolk, Ronald P. and Strauch, Konstantin and Stringham, Heather M. and Swertz, Morris A. and Swift, Amy J. and Tönjes, Anke and Tsafantakis, Emmanouil and Van Der Most, Peter J. and Van Vliet-Ostaptchouk, Jana V. and Vandenput, Liesbeth and Vartiainen, Erkki and Venturini, Cristina and Verweij, Niek and Viikari, Jorma S. and Vitart, Veronique and Vohl, Marie Claude and Vonk, Judith M. and Waeber, Gérard and Widén, Elisabeth and Willemsen, Gonneke and Wilsgaard, Tom and Winkler, Thomas W. and Wright, Alan F. and Yerges-Armstrong, Laura M. and Zhao, Jing Hua and Carola Zillikens, M. and Boomsma, Dorret I. and Bouchard, Claude and Chambers, John C. and Chasman, Daniel I. and Cusi, Daniele and Gansevoort, Ron T. and Gieger, Christian and Hansen, Torben and Hicks, Andrew A. and Hu, Frank and Hveem, Kristian and Jarvelin, Marjo Riitta and Kajantie, Eero and Kooner, Jaspal S. and Kuh, Diana and Kuusisto, Johanna and Laakso, Markku and Lakka, Timo A. and Lehtimäki, Terho and Metspalu, Andres and Njølstad, Inger and Ohlsson, Claes and Oldehinkel, Albertine J. and Palmer, Lyle J. and Pedersen, Oluf and Perola, Markus and Peters, Annette and Psaty, Bruce M. and Puolijoki, Hannu and Rauramaa, Rainer and Rudan, Igor and Salomaa, Veikko and Schwarz, Peter E H and Shudiner, Alan R. and Smit, Jan H. and Sørensen, Thorkild I A and Spector, Timothy D. and Stefansson, Kari and Stumvoll, Michael and Tremblay, Angelo and Tuomilehto, Jaakko and Uitterlinden, André G. and Uusitupa, Matti and Völker, Uwe and Vollenweider, Peter and Wareham, Nicholas J. and Watkins, Hugh and Wilson, James F. and Zeggini, Eleftheria and Abecasis, Goncalo R. and Boehnke, Michael and Borecki, Ingrid B. and Deloukas, Panos and Van Duijn, Cornelia M. and Fox, Caroline 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 Schlessinger, David and Thorsteinsdottir, Unnur and Strachan, David P. and Frayling, Timothy and Hirschhorn, Joel N. and Müller-Nurasyid, Martina and Loos, Ruth J F}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{11}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape}},
  url          = {{http://dx.doi.org/10.1038/ncomms13357}},
  doi          = {{10.1038/ncomms13357}},
  volume       = {{7}},
  year         = {{2016}},
}