Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.

Authors:
Dr Zoltán Kutalik, PhD
Dr Zoltán Kutalik, PhD
Institute of Social and Preventive Medicine, CHUV
Assistant Professor
Biostatistics
Lausanne, Vaud | Switzerland
Dr. Najaf Amin, PhD
Dr. Najaf Amin, PhD
Erasmus University Medical Center
Rotterdam | Netherlands
Sonja I Berndt Stefan Gustafsson Reedik Mägi Andrea Ganna Eleanor Wheeler Mary F Feitosa Anne E Justice Keri L Monda Damien C Croteau-Chonka Felix R Day Tõnu Esko Tove Fall Teresa Ferreira Davide Gentilini Anne U Jackson Jian'an Luan Joshua C Randall Sailaja Vedantam Cristen J Willer Thomas W Winkler Andrew R Wood Tsegaselassie Workalemahu Yi-Juan Hu Sang Hong Lee Liming Liang Dan-Yu Lin Josine L Min Benjamin M Neale Gudmar Thorleifsson Jian Yang Eva Albrecht Jennifer L Bragg-Gresham Gemma Cadby Martin den Heijer Niina Eklund Krista Fischer Anuj Goel Jouke-Jan Hottenga Jennifer E Huffman Ivonne Jarick Åsa Johansson Toby Johnson Stavroula Kanoni Marcus E Kleber Inke R König Kati Kristiansson Claudia Lamina Cecile Lecoeur Guo Li Massimo Mangino Wendy L McArdle Carolina Medina-Gomez Martina Müller-Nurasyid Julius S Ngwa Ilja M Nolte Lavinia Paternoster Sonali Pechlivanis Markus Perola Marjolein J Peters Michael Preuss Lynda M Rose Jianxin Shi Dmitry Shungin Albert Vernon Smith Rona J Strawbridge Ida Surakka Alexander Teumer Mieke D Trip Jonathan Tyrer Jana V Van Vliet-Ostaptchouk Liesbeth Vandenput Lindsay L Waite Jing Hua Zhao Devin Absher Folkert W Asselbergs Mustafa Atalay Antony P Attwood Anthony J Balmforth Hanneke Basart John Beilby Lori L Bonnycastle Paolo Brambilla Marcel Bruinenberg Harry Campbell Daniel I Chasman Peter S Chines Francis S Collins John M Connell William O Cookson Ulf de Faire Femmie de Vegt Mariano Dei Maria Dimitriou Sarah Edkins Karol Estrada David M Evans Martin Farrall Marco M Ferrario Jean Ferrières Lude Franke Francesca Frau Pablo V Gejman Harald Grallert Henrik Grönberg Vilmundur Gudnason Alistair S Hall Per Hall Anna-Liisa Hartikainen Caroline Hayward Nancy L Heard-Costa Andrew C Heath Johannes Hebebrand Georg Homuth Frank B Hu Sarah E Hunt Elina Hyppönen Carlos Iribarren Kevin B Jacobs John-Olov Jansson Antti Jula Mika Kähönen Sekar Kathiresan Frank Kee Kay-Tee Khaw Mika Kivimäki Wolfgang Koenig Aldi T Kraja Meena Kumari Kari Kuulasmaa Johanna Kuusisto Jaana H Laitinen Timo A Lakka Claudia Langenberg Lenore J Launer Lars Lind Jaana Lindström Jianjun Liu Antonio Liuzzi Marja-Liisa Lokki Mattias Lorentzon Pamela A Madden Patrik K Magnusson Paolo Manunta Diana Marek Winfried März Irene Mateo Leach Barbara McKnight Sarah E Medland Evelin Mihailov Lili Milani Grant W Montgomery Vincent Mooser Thomas W Mühleisen Patricia B Munroe Arthur W Musk Narisu Narisu Gerjan Navis George Nicholson Ellen A Nohr Ken K Ong Ben A Oostra Colin N A Palmer Aarno Palotie John F Peden Nancy Pedersen Annette Peters Ozren Polasek Anneli Pouta Peter P Pramstaller Inga Prokopenko Carolin Pütter Aparna Radhakrishnan Olli Raitakari Augusto Rendon Fernando Rivadeneira Igor Rudan Timo E Saaristo Jennifer G Sambrook Alan R Sanders Serena Sanna Jouko Saramies Sabine Schipf Stefan Schreiber Heribert Schunkert So-Youn Shin Stefano Signorini Juha Sinisalo Boris Skrobek Nicole Soranzo Alena Stančáková Klaus Stark Jonathan C Stephens Kathleen Stirrups Ronald P Stolk Michael Stumvoll Amy J Swift Eirini V Theodoraki Barbara Thorand David-Alexandre Tregouet Elena Tremoli Melanie M Van der Klauw Joyce B J van Meurs Sita H Vermeulen Jorma Viikari Jarmo Virtamo Veronique Vitart Gérard Waeber Zhaoming Wang Elisabeth Widén Sarah H Wild Gonneke Willemsen Bernhard R Winkelmann Jacqueline C M Witteman Bruce H R Wolffenbuttel Andrew Wong Alan F Wright M Carola Zillikens Philippe Amouyel Bernhard O Boehm Eric Boerwinkle Dorret I Boomsma Mark J Caulfield Stephen J Chanock L Adrienne Cupples Daniele Cusi George V Dedoussis Jeanette Erdmann Johan G Eriksson Paul W Franks Philippe Froguel Christian Gieger Ulf Gyllensten Anders Hamsten Tamara B Harris Christian Hengstenberg Andrew A Hicks Aroon Hingorani Anke Hinney Albert Hofman Kees G Hovingh Kristian Hveem Thomas Illig Marjo-Riitta Jarvelin Karl-Heinz Jöckel Sirkka M Keinanen-Kiukaanniemi Lambertus A Kiemeney Diana Kuh Markku Laakso Terho Lehtimäki Douglas F Levinson Nicholas G Martin Andres Metspalu Andrew D Morris Markku S Nieminen Inger Njølstad Claes Ohlsson Albertine J Oldehinkel Willem H Ouwehand Lyle J Palmer Brenda Penninx Chris Power Michael A Province Bruce M Psaty Lu Qi Rainer Rauramaa Paul M Ridker Samuli Ripatti Veikko Salomaa Nilesh J Samani Harold Snieder Thorkild I A Sørensen Timothy D Spector Kari Stefansson Anke Tönjes Jaakko Tuomilehto André G Uitterlinden Matti Uusitupa Pim van der Harst Peter Vollenweider Henri Wallaschofski Nicholas J Wareham Hugh Watkins H-Erich Wichmann James F Wilson Goncalo R Abecasis Themistocles L Assimes Inês Barroso Michael Boehnke Ingrid B Borecki Panos Deloukas Caroline S Fox Timothy Frayling Leif C Groop Talin Haritunian Iris M Heid David Hunter Robert C Kaplan Fredrik Karpe Miriam F Moffatt Karen L Mohlke Jeffrey R O'Connell Yudi Pawitan Eric E Schadt David Schlessinger Valgerdur Steinthorsdottir David P Strachan Unnur Thorsteinsdottir Cornelia M van Duijn Peter M Visscher Anna Maria Di Blasio Joel N Hirschhorn Cecilia M Lindgren Andrew P Morris David Meyre André Scherag Mark I McCarthy Elizabeth K Speliotes Kari E North Ruth J F Loos Erik Ingelsson

Nat Genet 2013 May 7;45(5):501-12. Epub 2013 Apr 7.

US Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

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http://dx.doi.org/10.1038/ng.2606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973018PMC
May 2013
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