Genetic studies of body mass index yield new insights for obesity biology.

Authors:
Dr Anubha Mahajan, PhD
Dr Anubha Mahajan, PhD
Wellcome Trust Centre for Human Genetics, University of Oxford
UK
Adam E Locke Bratati Kahali Sonja I Berndt Anne E Justice Tune H Pers Felix R Day Corey Powell Sailaja Vedantam Martin L Buchkovich Jian Yang Damien C Croteau-Chonka Tonu Esko Tove Fall Teresa Ferreira Stefan Gustafsson Zoltán Kutalik Jian'an Luan Reedik Mägi Joshua C Randall Thomas W Winkler Andrew R Wood Tsegaselassie Workalemahu Jessica D Faul Jennifer A Smith Jing Hua Zhao Wei Zhao Jin Chen Rudolf Fehrmann Åsa K Hedman Juha Karjalainen Ellen M Schmidt Devin Absher Najaf Amin Denise Anderson Marian Beekman Jennifer L Bolton Jennifer L Bragg-Gresham Steven Buyske Ayse Demirkan Guohong Deng Georg B Ehret Bjarke Feenstra Mary F Feitosa Krista Fischer Anuj Goel Jian Gong Anne U Jackson Stavroula Kanoni Marcus E Kleber Kati Kristiansson Unhee Lim Vaneet Lotay Massimo Mangino Irene Mateo Leach Carolina Medina-Gomez Sarah E Medland Michael A Nalls Cameron D Palmer Dorota Pasko Sonali Pechlivanis Marjolein J Peters Inga Prokopenko Dmitry Shungin Alena Stančáková Rona J Strawbridge Yun Ju Sung Toshiko Tanaka Alexander Teumer Stella Trompet Sander W van der Laan Jessica van Setten Jana V Van Vliet-Ostaptchouk Zhaoming Wang Loïc Yengo Weihua Zhang Aaron Isaacs Eva Albrecht Johan Ärnlöv Gillian M Arscott Antony P Attwood Stefania Bandinelli Amy Barrett Isabelita N Bas Claire Bellis Amanda J Bennett Christian Berne Roza Blagieva Matthias Blüher Stefan Böhringer Lori L Bonnycastle Yvonne Böttcher Heather A Boyd Marcel Bruinenberg Ida H Caspersen Yii-Der Ida Chen Robert Clarke E Warwick Daw Anton J M de Craen Graciela Delgado Maria Dimitriou Alex S F Doney Niina Eklund Karol Estrada Elodie Eury Lasse Folkersen Ross M Fraser Melissa E Garcia Frank Geller Vilmantas Giedraitis Bruna Gigante Alan S Go Alain Golay Alison H Goodall Scott D Gordon Mathias Gorski Hans-Jörgen Grabe Harald Grallert Tanja B Grammer Jürgen Gräßler Henrik Grönberg Christopher J Groves Gaëlle Gusto Jeffrey Haessler Per Hall Toomas Haller Goran Hallmans Catharina A Hartman Maija Hassinen Caroline Hayward Nancy L Heard-Costa Quinta Helmer Christian Hengstenberg Oddgeir Holmen Jouke-Jan Hottenga Alan L James Janina M Jeff Åsa Johansson Jennifer Jolley Thorhildur Juliusdottir Leena Kinnunen Wolfgang Koenig Markku Koskenvuo Wolfgang Kratzer Jaana Laitinen Claudia Lamina Karin Leander Nanette R Lee Peter Lichtner Lars Lind Jaana Lindström Ken Sin Lo Stéphane Lobbens Roberto Lorbeer Yingchang Lu François Mach Patrik K E Magnusson Wendy L McArdle Stela McLachlan Cristina Menni Sigrun Merger Evelin Mihailov Lili Milani Alireza Moayyeri Keri L Monda Mario A Morken Antonella Mulas Gabriele Müller Martina Müller-Nurasyid Arthur W Musk Ramaiah Nagaraja Markus M Nöthen Ilja M Nolte Stefan Pilz Nigel W Rayner Frida Renstrom Rainer Rettig Janina S Ried Stephan Ripke Neil R Robertson Lynda M Rose Serena Sanna Hubert Scharnagl Salome Scholtens Fredrick R Schumacher William R Scott Thomas Seufferlein Jianxin Shi Albert Vernon Smith Joanna Smolonska Alice V Stanton Valgerdur Steinthorsdottir Kathleen Stirrups Heather M Stringham Johan Sundström Morris A Swertz Amy J Swift Ann-Christine Syvänen Sian-Tsung Tan Bamidele O Tayo Barbara Thorand Gudmar Thorleifsson Jonathan P Tyrer Hae-Won Uh Liesbeth Vandenput Frank C Verhulst Sita H Vermeulen Niek Verweij Judith M Vonk Lindsay L Waite Helen R Warren Dawn Waterworth Michael N Weedon Lynne R Wilkens Christina Willenborg Tom Wilsgaard Mary K Wojczynski Andrew Wong Alan F Wright Qunyuan Zhang Eoin P Brennan Murim Choi Zari Dastani Alexander W Drong Per Eriksson Anders Franco-Cereceda Jesper R Gådin Ali G Gharavi Michael E Goddard Robert E Handsaker Jinyan Huang Fredrik Karpe Sekar Kathiresan Sarah Keildson Krzysztof Kiryluk Michiaki Kubo Jong-Young Lee Liming Liang Richard P Lifton Baoshan Ma Steven A McCarroll Amy J McKnight Josine L Min Miriam F Moffatt Grant W Montgomery Joanne M Murabito George Nicholson Dale R Nyholt Yukinori Okada John R B Perry Rajkumar Dorajoo Eva Reinmaa Rany M Salem Niina Sandholm Robert A Scott Lisette Stolk Atsushi Takahashi Toshihiro Tanaka Ferdinand M van 't Hooft Anna A E Vinkhuyzen Harm-Jan Westra Wei Zheng Krina T Zondervan Andrew C Heath Dominique Arveiler Stephan J L Bakker John Beilby Richard N Bergman John Blangero Pascal Bovet Harry Campbell Mark J Caulfield Giancarlo Cesana Aravinda Chakravarti Daniel I Chasman Peter S Chines Francis S Collins Dana C Crawford L Adrienne Cupples Daniele Cusi John Danesh Ulf de Faire Hester M den Ruijter Anna F Dominiczak Raimund Erbel Jeanette Erdmann Johan G Eriksson Martin Farrall Stephan B Felix Ele Ferrannini Jean Ferrières Ian Ford Nita G Forouhi Terrence Forrester Oscar H Franco Ron T Gansevoort Pablo V Gejman Christian Gieger Omri Gottesman Vilmundur Gudnason Ulf Gyllensten Alistair S Hall Tamara B Harris Andrew T Hattersley Andrew A Hicks Lucia A Hindorff Aroon D Hingorani Albert Hofman Georg Homuth G Kees Hovingh Steve E Humphries Steven C Hunt Elina Hyppönen Thomas Illig Kevin B Jacobs Marjo-Riitta Jarvelin Karl-Heinz Jöckel Berit Johansen Pekka Jousilahti J Wouter Jukema Antti M Jula Jaakko Kaprio John J P Kastelein Sirkka M Keinanen-Kiukaanniemi Lambertus A Kiemeney Paul Knekt Jaspal S Kooner Charles Kooperberg Peter Kovacs Aldi T Kraja Meena Kumari 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 Frans L Moll Andrew D Morris Andrew P Morris Jeffrey C Murray Mari Nelis Claes Ohlsson Albertine J Oldehinkel Ken K Ong Pamela A F Madden Gerard Pasterkamp John F Peden Annette Peters Dirkje S Postma Peter P Pramstaller Jackie F Price Lu Qi Olli T Raitakari Tuomo Rankinen D C Rao Treva K Rice Paul M Ridker John D Rioux Marylyn D Ritchie Igor Rudan Veikko Salomaa Nilesh J Samani Jouko Saramies Mark A Sarzynski Heribert Schunkert Peter E H Schwarz Peter Sever Alan R Shuldiner Juha Sinisalo Ronald P Stolk Konstantin Strauch Anke Tönjes David-Alexandre Trégouët Angelo Tremblay Elena Tremoli Jarmo Virtamo Marie-Claude Vohl Uwe Völker Gérard Waeber Gonneke Willemsen Jacqueline C Witteman M Carola Zillikens Linda S Adair Philippe Amouyel Folkert W Asselbergs Themistocles L Assimes Murielle Bochud Bernhard O Boehm Eric Boerwinkle Stefan R Bornstein Erwin P Bottinger Claude Bouchard Stéphane Cauchi John C Chambers Stephen J Chanock Richard S Cooper Paul I W de Bakker George Dedoussis Luigi Ferrucci Paul W Franks Philippe Froguel Leif C Groop Christopher A Haiman Anders Hamsten Jennie Hui David J Hunter Kristian Hveem Robert C Kaplan Mika Kivimaki Diana Kuh Markku Laakso Yongmei Liu Nicholas G Martin Winfried März Mads Melbye Andres Metspalu Susanne Moebus Patricia B Munroe Inger Njølstad Ben A Oostra Colin N A Palmer Nancy L Pedersen Markus Perola Louis Pérusse Ulrike Peters Chris Power Thomas Quertermous Rainer Rauramaa Fernando Rivadeneira Timo E Saaristo Danish Saleheen Naveed Sattar Eric E Schadt David Schlessinger P Eline Slagboom Harold Snieder Tim D Spector Unnur Thorsteinsdottir Michael Stumvoll Jaakko Tuomilehto André G Uitterlinden Matti Uusitupa Pim van der Harst Mark Walker Henri Wallaschofski Nicholas J Wareham Hugh Watkins David R Weir H-Erich Wichmann James F Wilson Pieter Zanen Ingrid B Borecki Panos Deloukas Caroline S Fox Iris M Heid Jeffrey R O'Connell David P Strachan Kari Stefansson Cornelia M van Duijn Gonçalo R Abecasis Lude Franke Timothy M Frayling Mark I McCarthy Peter M Visscher André Scherag Cristen J Willer Michael Boehnke Karen L Mohlke Cecilia M Lindgren Jacques S Beckmann Inês Barroso Kari E North Erik Ingelsson Joel N Hirschhorn Ruth J F Loos Elizabeth K Speliotes

Nature 2015 Feb;518(7538):197-206

Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

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February 2015
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References

(Supplied by CrossRef)
Article in Behav. Genet.
HH Maes et al.
Behav. Genet. 1997
Article in Am. J. Hum. Genet.
PM Visscher et al.
Am. J. Hum. Genet. 2012
Article in PLoS Genet.
N Zaitlen et al.
PLoS Genet. 2013
Article in Mol. Cell. Endocrinol.
T Fall et al.
Mol. Cell. Endocrinol. 2014
Article in Nature Genet.
EK Speliotes et al.
Nature Genet. 2010
Article in Nature Genet.
CJ Willer et al.
Nature Genet. 2009
Article in PLoS Genet.
BF Voight et al.
PLoS Genet. 2012
Article in Nature Genet.
TO Kilpeläinen et al.
Nature Genet. 2011
Article in Nature Genet.
JP Bradfield et al.
Nature Genet. 2012
Article in Nature Genet.
KL Monda et al.
Nature Genet. 2013
Article in Nature Genet.
SI Berndt et al.
Nature Genet. 2013

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