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

Author:
  • 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
  • Anubha Mahajan
  • 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 Renström
  • 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 Franks
  • Philippe Froguel
  • Leif 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
Publishing year: 2015
Language: English
Pages: 197-401
Publication/Series: Nature
Volume: 518
Issue: 7538
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Endocrinology and Diabetes
  • Polymorphism
  • Obesity: metabolism
  • Obesity: genetics
  • Insulin: secretion
  • Insulin: metabolism
  • Glutamic Acid: metabolism
  • Genetic Predisposition to Disease: genetics
  • Europe: ethnology
  • Energy Metabolism: genetics
  • Continental Population Groups: genetics
  • Adipogenesis: genetics
  • Adiposity: genetics
  • Single Nucleotide: genetics
  • Quantitative Trait Loci: genetics
  • Synapses: metabolism

Other

Published
  • Diabetes and Endocrinology
  • Genetic and Molecular Epidemiology
  • ISSN: 0028-0836
Paul Franks
E-mail: paul [dot] franks [at] med [dot] lu [dot] se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49

60-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00