New genetic loci link adipose and insulin biology to body fat distribution.

Authors:
Dmitry Shungin
Dmitry Shungin
Lund University Diabetes Center
Lund | Sweden
Thomas W Winkler
Thomas W Winkler
Regensburg University Medical Center
Germany
Damien C Croteau-Chonka
Damien C Croteau-Chonka
University of North Carolina
United States
Teresa Ferreira
Teresa Ferreira
Hospital Pulido Valente
Portugal
Adam E Locke
Adam E Locke
Emory University
United States
Rona J Strawbridge
Rona J Strawbridge
University of Michigan
United States
Tune H Pers
Tune H Pers
Technical University of Denmark
Denmark
Krista Fischer Anne E Justice Tsegaselassie Workalemahu Joseph M W Wu Martin L Buchkovich Nancy L Heard-Costa Tamara S Roman Alexander W Drong Ci Song Stefan Gustafsson Felix R Day Tonu Esko Tove Fall Zoltán Kutalik Jian'an Luan Joshua C Randall André Scherag Sailaja Vedantam Andrew R Wood Jin Chen Rudolf Fehrmann Juha Karjalainen Bratati Kahali Ching-Ti Liu Ellen M Schmidt Devin Absher Najaf Amin Denise Anderson Marian Beekman Jennifer L Bragg-Gresham Steven Buyske Ayse Demirkan Georg B Ehret Mary F Feitosa Anuj Goel Anne U Jackson Toby Johnson Marcus E Kleber Kati Kristiansson Massimo Mangino Irene Mateo Leach Carolina Medina-Gomez Cameron D Palmer Dorota Pasko Sonali Pechlivanis Marjolein J Peters Inga Prokopenko Alena Stančáková Yun Ju Sung Toshiko Tanaka Alexander Teumer Jana V Van Vliet-Ostaptchouk Loïc Yengo Weihua Zhang Eva Albrecht Johan Ärnlöv Gillian M Arscott Stefania Bandinelli Amy Barrett Claire Bellis Amanda J Bennett Christian Berne Matthias Blüher Stefan Böhringer Fabrice Bonnet Yvonne Böttcher Marcel Bruinenberg Delia B Carba Ida H Caspersen Robert Clarke E Warwick Daw Joris Deelen Ewa Deelman Graciela Delgado Alex Sf Doney Niina Eklund Michael R Erdos Karol Estrada Elodie Eury Nele Friedrich Melissa E Garcia Vilmantas Giedraitis Bruna Gigante Alan S Go Alain Golay Harald Grallert Tanja B Grammer Jürgen Gräßler Jagvir Grewal Christopher J Groves Toomas Haller Goran Hallmans Catharina A Hartman Maija Hassinen Caroline Hayward Kauko Heikkilä Karl-Heinz Herzig Quinta Helmer Hans L Hillege Oddgeir Holmen Steven C Hunt Aaron Isaacs Till Ittermann Alan L James Ingegerd Johansson Thorhildur Juliusdottir Ioanna-Panagiota Kalafati Leena Kinnunen Wolfgang Koenig Ishminder K Kooner Wolfgang Kratzer Claudia Lamina Karin Leander Nanette R Lee Peter Lichtner Lars Lind Jaana Lindström Stéphane Lobbens Mattias Lorentzon François Mach Patrik Ke Magnusson Anubha Mahajan Wendy L McArdle Cristina Menni Sigrun Merger Evelin Mihailov Lili Milani Rebecca Mills Alireza Moayyeri Keri L Monda Simon P Mooijaart Thomas W Mühleisen Antonella Mulas Gabriele Müller Martina Müller-Nurasyid Ramaiah Nagaraja Michael A Nalls Narisu Narisu Nicola Glorioso Ilja M Nolte Matthias Olden Nigel W Rayner Frida Renstrom Janina S Ried Neil R Robertson Lynda M Rose Serena Sanna Hubert Scharnagl Salome Scholtens Bengt Sennblad Thomas Seufferlein Colleen M Sitlani Albert Vernon Smith Kathleen Stirrups Heather M Stringham Johan Sundström Morris A Swertz Amy J Swift Ann-Christine Syvänen Bamidele O Tayo Barbara Thorand Gudmar Thorleifsson Andreas Tomaschitz Chiara Troffa Floor Va van Oort Niek Verweij Judith M Vonk Lindsay L Waite Roman Wennauer Tom Wilsgaard Mary K Wojczynski Andrew Wong Qunyuan Zhang Jing Hua Zhao Eoin P Brennan Murim Choi Per Eriksson Lasse Folkersen Anders Franco-Cereceda Ali G Gharavi Åsa K Hedman Marie-France Hivert Jinyan Huang Stavroula Kanoni Fredrik Karpe Sarah Keildson Krzysztof Kiryluk Liming Liang Richard P Lifton Baoshan Ma Amy J McKnight Ruth McPherson Andres Metspalu Josine L Min Miriam F Moffatt Grant W Montgomery Joanne M Murabito George Nicholson Dale R Nyholt Christian Olsson John Rb Perry Eva Reinmaa Rany M Salem Niina Sandholm Eric E Schadt Robert A Scott Lisette Stolk Edgar E Vallejo Harm-Jan Westra Krina T Zondervan Philippe Amouyel Dominique Arveiler Stephan Jl Bakker John Beilby Richard N Bergman John Blangero Morris J Brown Michel Burnier Harry Campbell Aravinda Chakravarti Peter S Chines Simone Claudi-Boehm Francis S Collins Dana C Crawford John Danesh Ulf de Faire Eco Jc de Geus Marcus Dörr Raimund Erbel Johan G Eriksson Martin Farrall Ele Ferrannini Jean Ferrières Nita G Forouhi Terrence Forrester Oscar H Franco Ron T Gansevoort Christian Gieger Vilmundur Gudnason Christopher A Haiman Tamara B Harris Andrew T Hattersley Markku Heliövaara Andrew A Hicks Aroon D Hingorani Wolfgang Hoffmann Albert Hofman Georg Homuth Steve E Humphries Elina Hyppönen Thomas Illig Marjo-Riitta Jarvelin Berit Johansen Pekka Jousilahti Antti M Jula Jaakko Kaprio Frank Kee Sirkka M Keinanen-Kiukaanniemi Jaspal S Kooner Charles Kooperberg Peter Kovacs Aldi T Kraja Meena Kumari Kari Kuulasmaa Johanna Kuusisto Timo A Lakka Claudia Langenberg Loic Le Marchand Terho Lehtimäki Valeriya Lyssenko Satu Männistö André Marette Tara C Matise Colin A McKenzie Barbara McKnight Arthur W Musk Stefan Möhlenkamp Andrew D Morris Mari Nelis Claes Ohlsson Albertine J Oldehinkel Ken K Ong Lyle J Palmer Brenda W Penninx Annette Peters Peter P Pramstaller Olli T Raitakari Tuomo Rankinen D C Rao Treva K Rice Paul M Ridker Marylyn D Ritchie Igor Rudan Veikko Salomaa Nilesh J Samani Jouko Saramies Mark A Sarzynski Peter Eh Schwarz Alan R Shuldiner Jan A Staessen Valgerdur Steinthorsdottir Ronald P Stolk Konstantin Strauch Anke Tönjes Angelo Tremblay Elena Tremoli Marie-Claude Vohl Uwe Völker Peter Vollenweider James F Wilson Jacqueline C Witteman Linda S Adair Murielle Bochud Bernhard O Boehm Stefan R Bornstein Claude Bouchard Stéphane Cauchi Mark J Caulfield John C Chambers Daniel I Chasman Richard S Cooper George Dedoussis Luigi Ferrucci Philippe Froguel Hans-Jörgen Grabe Anders Hamsten Jennie Hui Kristian Hveem Karl-Heinz Jöckel Mika Kivimaki Diana Kuh Markku Laakso Yongmei Liu Winfried März Patricia B Munroe Inger Njølstad Ben A Oostra Colin Na Palmer Nancy L Pedersen Markus Perola Louis Pérusse Ulrike Peters Chris Power Thomas Quertermous Rainer Rauramaa Fernando Rivadeneira Timo E Saaristo Danish Saleheen Juha Sinisalo P Eline Slagboom Harold Snieder Tim D Spector Kari Stefansson Michael Stumvoll Jaakko Tuomilehto André G Uitterlinden Matti Uusitupa Pim van der Harst Giovanni Veronesi Mark Walker Nicholas J Wareham Hugh Watkins H-Erich Wichmann Goncalo R Abecasis Themistocles L Assimes Sonja I Berndt Michael Boehnke Ingrid B Borecki Panos Deloukas Lude Franke Timothy M Frayling Leif C Groop David J Hunter Robert C Kaplan Jeffrey R O'Connell Lu Qi David Schlessinger David P Strachan Unnur Thorsteinsdottir Cornelia M van Duijn Cristen J Willer Peter M Visscher Jian Yang Joel N Hirschhorn M Carola Zillikens Mark I McCarthy Elizabeth K Speliotes Kari E North Caroline S Fox Inês Barroso Paul W Franks Erik Ingelsson Iris M Heid Ruth Jf Loos L Adrienne Cupples Andrew P Morris Cecilia M Lindgren Karen L Mohlke

Nature 2015 Feb;518(7538):187-196

Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

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February 2015
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