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

Janina S Ried; Janina Jeff M; Audrey Y Chu; Jennifer L Bragg-Gresham; Jenny van Dongen; Jennifer E Huffman; Tarunveer S Ahluwalia; Gemma Cadby; Niina Eklund; Joel Eriksson; +266 more... Tõnu Esko; Mary F Feitosa; Anuj Goel ORCID logo; Mathias Gorski; Caroline Hayward; Nancy L Heard-Costa; Anne U Jackson ORCID logo; Eero Jokinen; Stavroula Kanoni; Kati Kristiansson ORCID logo; Zoltán Kutalik; Jari Lahti; Jian'an Luan; Reedik Mägi; Anubha Mahajan; Massimo Mangino; Carolina Medina-Gomez ORCID logo; Keri L Monda; Ilja M Nolte ORCID logo; Louis Pérusse; Inga Prokopenko ORCID logo; Lu Qi; Lynda M Rose; Erika Salvi; Megan T Smith; Harold Snieder; Alena Stančáková; Yun Ju Sung; Ioanna Tachmazidou; Alexander Teumer ORCID logo; Gudmar Thorleifsson; Pim van der Harst; Ryan W Walker; Sophie R Wang; Sarah H Wild; Sara M Willems; Andrew Wong ORCID logo; Weihua Zhang; Eva Albrecht; Alexessander Couto Alves; Stephan JL Bakker; Cristina Barlassina; Traci M Bartz; John Beilby ORCID logo; Claire Bellis; Richard N Bergman; Sven Bergmann ORCID logo; John Blangero; Matthias Blüher; Eric Boerwinkle; Lori L Bonnycastle; Stefan R Bornstein; Marcel Bruinenberg; Harry Campbell; Yii-Der Ida Chen; Charleston WK Chiang; Peter S Chines; Francis S Collins; Fracensco Cucca; L Adrienne Cupples; Francesca D'Avila; Eco JC 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 Harder; Catharina A Hartman; Maija Hassinen; Nicholas Hastie; Andrew Tym Hattersley; 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 Justesen; Anne E Justice; Mika Kähönen; Maria Karaleftheri; Kay Tee Khaw; Sirkka M Keinanen-Kiukaanniemi; 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 ORCID logo; 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; DC 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 Steinthorsdottir; Kathleen Stirrups; Ronald P Stolk; Konstantin Strauch; Heather M Stringham; Morris A Swertz; Amy J Swift; Anke Tönjes; Emmanouil Tsafantakis; Peter J van der Most; Jana V Van Vliet-Ostaptchouk; 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-Armstrong; 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 Jarvelin; Eero Kajantie; Jaspal S Kooner; Diana Kuh; Johanna Kuusisto; Markku Laakso; Timo A Lakka; Terho Lehtimäki; Andres Metspalu; Inger Njølstad; Claes Ohlsson; Albertine J Oldehinkel; Lyle J Palmer; Oluf Pedersen; Markus Perola; Annette Peters; Bruce M Psaty; Hannu Puolijoki; Rainer Rauramaa; Igor Rudan; Veikko Salomaa; Peter EH Schwarz; Alan R Shudiner; Jan H Smit; Thorkild IA Sørensen; Timothy D Spector; Kari Stefansson; Michael Stumvoll; Angelo Tremblay; Jaakko Tuomilehto; André G Uitterlinden; 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 Duijn; 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 Thorsteinsdottir; David P Strachan ORCID logo; Timothy Frayling; Joel N Hirschhorn; Martina Müller-Nurasyid; Ruth JF Loos; (2016) A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape. Nature communications, 7 (1). 13357-. ISSN 2041-1723 DOI: 10.1038/ncomms13357
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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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