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

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Ried , J S , Jeff , J M , Chu , A Y , Bragg-Gresham , J L , van Dongen , J , Huffman , J E , Ahluwalia , T 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 , Kristiansson , K , Kutalik , Z , Lahti , J , Luan , J , Maegi , R , Mahajan , A , Mangino , M , Medina-Gomez , C , Monda , K L , Nolte , I M , Perusse , L , Prokopenko , I , Qi , L , Rose , L M , Salvi , E , Smith , M T , Snieder , H , Stancakova , A , Sung , Y J , Tachmazidou , I , Teumer , A , Thorleifsson , G , van der Harst , P , Walker , R W , Wang , S R , Wild , S H , Willems , S M , Wong , A , Zhang , W , Albrecht , E , Alves , A C , Bakker , S J L , Barlassina , C , Bartz , T M , Beilby , J , Bellis , C , Bergman , R N , Bergmann , S , Blangero , J , Blueher , M , Boerwinkle , E , Bonnycastle , L L , Bornstein , S R , Bruinenberg , M , Campbell , H , Chen , Y-D I , Chiang , C W K , Chines , P S , Collins , F S , Cucca , F , Cupples , L A , D'Avila , F , de Geus , E J C , Dedoussis , G , Dimitriou , M , Doering , A , Eriksson , J G , Farmaki , A-E , Farrall , M , Ferreira , T , Fischer , K , Forouhi , N G , Friedrich , N , Gjesing , A P , Glorioso , N , Graff , M , Grallert , H , Grarup , N , Graessler , J , Grewal , J , Hamsten , A , Harder , M N , Hartman , C A , Hassinen , M , Hastie , N , Hattersley , A T , Havulinna , A S , Heliovaara , M , Hillege , H , Hofman , A , Holmen , O , Homuth , G , Hottenga , J-J , Hui , J , Husemoen , L L , Hysi , P G , Isaacs , A , Ittermann , T , Jalilzadeh , S , James , A L , Jorgensen , T , Jousilahti , P , Jula , A , Justesen , J M , Justice , A E , Kahonen , M , Karaleftheri , M , Khaw , K T , Keinanen-Kiukaanniemi , S M , Kinnunen , L , Knekt , P B , Koistinen , H A , Kolcic , I , Kooner , I K , Koskinen , S , Kovacs , P , Kyriakou , T , Laitinen , T , Langenberg , C , Lewin , A M , Lichtner , P , Lindgren , C M , Lindstrom , J , Linneberg , A , Lorbeer , R , Lorentzon , M , Luben , R , Lyssenko , V , Mannisto , S , Manunta , P , Leach , I M , McArdle , W L , Mcknight , B , Mohlke , K L , Mihailov , E , Milani , L , Mills , R , Montasser , M E , Morris , A P , Mueller , G , Musk , A W , Narisu , N , Ong , K K , Oostra , B A , Osmond , C , Palotie , A , Pankow , J S , Paternoster , L , Penninx , B W , Pichler , I , Pilia , M G , Polasek , O , Pramstaller , P P , Raitakari , O T , Rankinen , T , Rao , D C , Rayner , N W , Ribel-Madsen , R , Rice , T K , Richards , M , Ridker , P M , Rivadeneira , F , Ryan , K A , Sanna , S , Sarzynski , M A , Scholtens , S , Scott , R A , Sebert , S , Southam , L , Sparso , T H , Steinthorsdottir , V , Stirrups , K , Stolk , R P , Strauch , K , Stringham , H M , Swertz , M A , Swift , A J , Toenjes , A , Tsafantakis , E , van der Most , P J , Van Vliet-Ostaptchouk , J V , Vandenput , L , Vartiainen , E , Venturini , C , Verweij , N , Viikari , J S , Vitart , V , Vohl , M-C , Vonk , J M , Waeber , G , Widen , E , Willemsen , G , Wilsgaard , T , Winkler , T W , Wright , A F , Yerges-Armstrong , L M , Zhao , J H , Zillikens , M C , Boomsma , D I , Bouchard , C , Chambers , J C , Chasman , D I , Cusi , D , Gansevoort , R T , Gieger , C , Hansen , T , Hicks , A A , Hu , F , Hveem , K , Jarvelin , M-R , Kajantie , E , Kooner , J S , Kuh , D , Kuusisto , J , Laakso , M , Lakka , T A , Lehtimaeki , T , Metspalu , A , Njolstad , I , Ohlsson , C , Oldehinkel , A J , Palmer , L J , Pedersen , O , Perola , M , Peters , A , Psaty , B M , Puolijoki , H , Rauramaa , R , Rudan , I , Salomaa , V , Schwarz , P E H , Shudiner , A R , Smit , J H , Sorensen , T I A , Spector , T D , Stefansson , K , Stumvoll , M , Tremblay , A , Tuomilehto , J , Uitterlinden , A G , Uusitupa , M , Voelker , U , Vollenweider , P , Wareham , N J , Watkins , H , Wilson , J F , Zeggini , E , Abecasis , G R , Boehnke , M , Borecki , I B , Deloukas , P , van Duijn , C M , Fox , C , Groop , L C , Heid , I M , Hunter , D J , Kaplan , R C , McCarthy , M I , North , K E , O'Connell , J R , Schlessinger , D , Thorsteinsdottir , U , Strachan , D P , Frayling , T , Hirschhorn , J N , Mueller-Nurasyid , M & Loos , R J F 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

Title: A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
Author: 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.
Contributor: University of Helsinki, Children's Hospital
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Behavioural Sciences
University of Helsinki, Clinicum
University of Helsinki, Complex Disease Genetics
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Children's Hospital
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, University of Washington Seattle
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2016-11-23
Language: eng
Number of pages: 11
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/173091
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.
Subject: GENOME-WIDE ASSOCIATION
DIET-INDUCED OBESITY
MASS INDEX
DISEASE ASSOCIATIONS
FAT DISTRIBUTION
EARLY-ONSET
HIP RATIO
RESOURCE
BIOLOGY
HEIGHT
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
515 Psychology
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