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

• DOI: 10.1038/ncomms13357
• Publication Date: 2016-11-23T10:39:24Z
• Authors: Janina S. Ried; Janina Jeff M.; Audrey Y. Chu; Jennifer L. Bragg...; Jenny van Dongen; Jennifer E. Huffman; Tarunveer S. Ahlu...; 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-G...; 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 Cout...; 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. ...; 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 Prior Gjesing; Nicola Glorioso; Mariaelisa Graff; Harald Grallert; Niels Grarup; Jürgen Gräßler; Jagvir Grewal; Anders Hamsten; Marie Neergaard H...; Catharina A. Hartman; Maija Hassinen; Nicholas Hastie; Andrew Tym Hatter...; 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 Jus...; Anne E. Justice; Mika Kähönen; Maria Karaleftheri; Kay Tee Khaw; Sirkka M. Keinane...; 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 Steinth...; Kathleen Stirrups; Ronald P. Stolk; Konstantin Strauch; Heather M. Stringham; Morris A. Swertz; Amy J. Swift; Anke Tönjes; Emmanouil Tsafant...; Peter J. van der ...; Jana V. Van Vliet...; 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-A...; 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 Jarv...; Eero Kajantie; Jaspal S. Kooner; Diana Kuh; Johanna Kuusisto; Markku Laakso; Timo A. Lakka; Terho Lehtimäki; Andres Metspalu; Inger Njølstad; Claes Ohlsson; Albertine J. Olde...; 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. Sø...; Timothy D. Spector; Kari Stefansson; Michael Stumvoll; Angelo Tremblay; Jaakko Tuomilehto; André G. Uitterli...; 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 D...; 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 Thorsteinsd...; David P. Strachan; Timothy Frayling; Joel N. Hirschhorn; Martina Müller-Nu...; Ruth J. F. Loos
• Keywords: Netherlands Twin Register (NTR); Statistical methods; Genome-wide association studies; 796; Mice; HEIGHT; Models; Psychology; Body Size; 2. Zero hunger; Principal Component Analysis; 0303 health sciences; Genome-wide association; Early-onset; VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801; Anthropometry; Mass index; Diet-induced obesity; Q; General medicine, internal medicine and other clinical medicine; Common; gene, body, shape; Multidisciplinary Sciences; Wessex Classification Subject Headings::Endocrinology::Diabetes; statistical methods; Science & Technology - Other Topics; Resource; 570; DIET-INDUCED OBESITY; EMC NIHES-01-64-02; Genotype; Science; EARLY-ONSET; 610; Snp; BIOLOGY; HIP RATIO; Genome-wide association studies Statistical methods; Article; 03 medical and health sciences; MASS INDEX; Genetic; genome-wide associations studies; DISEASE ASSOCIATIONS; RESOURCE; MD Multidisciplinary; Journal Article; Humans; GENOME-WIDE ASSOCIATION; Science & Technology; Models, Genetic; ta1184; Hip ratio; FAT DISTRIBUTION; ta3121; Biomedicine; EMC MM-01-39-09-A; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all); VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801; Genome-Wide Association Study

AbstractLarge 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.