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

Authors:
Dr Anubha Mahajan, PhD
Dr Anubha Mahajan, PhD
Wellcome Trust Centre for Human Genetics, University of Oxford
UK
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 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 Massimo Mangino Carolina Medina-Gomez 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 Couto Alves 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 Chiang 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 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 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 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 E H Schwarz Alan R Shudiner Jan H Smit Thorkild I A 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 Timothy Frayling Joel N Hirschhorn Martina Müller-Nurasyid Ruth J F Loos

Nat Commun 2016 11 23;7:13357. Epub 2016 Nov 23.

The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

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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http://dx.doi.org/10.1038/ncomms13357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114527PMC
November 2016
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