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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

ABSTRACT: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ? 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10??), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

SUBMITTER: Speliotes EK 

PROVIDER: S-EPMC3014648 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

Speliotes Elizabeth K EK   Willer Cristen J CJ   Berndt Sonja I SI   Monda Keri L KL   Thorleifsson Gudmar G   Jackson Anne U AU   Lango Allen Hana H   Lindgren Cecilia M CM   Luan Jian'an J   Mägi Reedik R   Randall Joshua C JC   Vedantam Sailaja S   Winkler Thomas W TW   Qi Lu L   Workalemahu Tsegaselassie T   Heid Iris M IM   Steinthorsdottir Valgerdur V   Stringham Heather M HM   Weedon Michael N MN   Wheeler Eleanor E   Wood Andrew R AR   Ferreira Teresa T   Weyant Robert J RJ   Segrè Ayellet V AV   Estrada Karol K   Liang Liming L   Nemesh James J   Park Ju-Hyun JH   Gustafsson Stefan S   Kilpeläinen Tuomas O TO   Yang Jian J   Bouatia-Naji Nabila N   Esko Tõnu T   Feitosa Mary F MF   Kutalik Zoltán Z   Mangino Massimo M   Raychaudhuri Soumya S   Scherag Andre A   Smith Albert Vernon AV   Welch Ryan R   Zhao Jing Hua JH   Aben Katja K KK   Absher Devin M DM   Amin Najaf N   Dixon Anna L AL   Fisher Eva E   Glazer Nicole L NL   Goddard Michael E ME   Heard-Costa Nancy L NL   Hoesel Volker V   Hottenga Jouke-Jan JJ   Johansson Asa A   Johnson Toby T   Ketkar Shamika S   Lamina Claudia C   Li Shengxu S   Moffatt Miriam F MF   Myers Richard H RH   Narisu Narisu N   Perry John R B JR   Peters Marjolein J MJ   Preuss Michael M   Ripatti Samuli S   Rivadeneira Fernando F   Sandholt Camilla C   Scott Laura J LJ   Timpson Nicholas J NJ   Tyrer Jonathan P JP   van Wingerden Sophie S   Watanabe Richard M RM   White Charles C CC   Wiklund Fredrik F   Barlassina Christina C   Chasman Daniel I DI   Cooper Matthew N MN   Jansson John-Olov JO   Lawrence Robert W RW   Pellikka Niina N   Prokopenko Inga I   Shi Jianxin J   Thiering Elisabeth E   Alavere Helene H   Alibrandi Maria T S MT   Almgren Peter P   Arnold Alice M AM   Aspelund Thor T   Atwood Larry D LD   Balkau Beverley B   Balmforth Anthony J AJ   Bennett Amanda J AJ   Ben-Shlomo Yoav Y   Bergman Richard N RN   Bergmann Sven S   Biebermann Heike H   Blakemore Alexandra I F AI   Boes Tanja T   Bonnycastle Lori L LL   Bornstein Stefan R SR   Brown Morris J MJ   Buchanan Thomas A TA   Busonero Fabio F   Campbell Harry H   Cappuccio Francesco P FP   Cavalcanti-Proença Christine C   Chen Yii-Der Ida YD   Chen Chih-Mei CM   Chines Peter S PS   Clarke Robert R   Coin Lachlan L   Connell John J   Day Ian N M IN   den Heijer Martin M   Duan Jubao J   Ebrahim Shah S   Elliott Paul P   Elosua Roberto R   Eiriksdottir Gudny G   Erdos Michael R MR   Eriksson Johan G JG   Facheris Maurizio F MF   Felix Stephan B SB   Fischer-Posovszky Pamela P   Folsom Aaron R AR   Friedrich Nele N   Freimer Nelson B NB   Fu Mao M   Gaget Stefan S   Gejman Pablo V PV   Geus Eco J C EJ   Gieger Christian C   Gjesing Anette P AP   Goel Anuj A   Goyette Philippe P   Grallert Harald H   Grässler Jürgen J   Greenawalt Danielle M DM   Groves Christopher J CJ   Gudnason Vilmundur V   Guiducci Candace C   Hartikainen Anna-Liisa AL   Hassanali Neelam N   Hall Alistair S AS   Havulinna Aki S AS   Hayward Caroline C   Heath Andrew C AC   Hengstenberg Christian C   Hicks Andrew A AA   Hinney Anke A   Hofman Albert A   Homuth Georg G   Hui Jennie J   Igl Wilmar W   Iribarren Carlos C   Isomaa Bo B   Jacobs Kevin B KB   Jarick Ivonne I   Jewell Elizabeth E   John Ulrich U   Jørgensen Torben T   Jousilahti Pekka P   Jula Antti A   Kaakinen Marika M   Kajantie Eero E   Kaplan Lee M LM   Kathiresan Sekar S   Kettunen Johannes J   Kinnunen Leena L   Knowles Joshua W JW   Kolcic Ivana I   König Inke R IR   Koskinen Seppo S   Kovacs Peter P   Kuusisto Johanna J   Kraft Peter P   Kvaløy Kirsti K   Laitinen Jaana J   Lantieri Olivier O   Lanzani Chiara C   Launer Lenore J LJ   Lecoeur Cecile C   Lehtimäki Terho T   Lettre Guillaume G   Liu Jianjun J   Lokki Marja-Liisa ML   Lorentzon Mattias M   Luben Robert N RN   Ludwig Barbara B   Manunta Paolo P   Marek Diana D   Marre Michel M   Martin Nicholas G NG   McArdle Wendy L WL   McCarthy Anne A   McKnight Barbara B   Meitinger Thomas T   Melander Olle O   Meyre David D   Midthjell Kristian K   Montgomery Grant W GW   Morken Mario A MA   Morris Andrew P AP   Mulic Rosanda R   Ngwa Julius S JS   Nelis Mari M   Neville Matt J MJ   Nyholt Dale R DR   O'Donnell Christopher J CJ   O'Rahilly Stephen S   Ong Ken K KK   Oostra Ben B   Paré Guillaume G   Parker Alex N AN   Perola Markus M   Pichler Irene I   Pietiläinen Kirsi H KH   Platou Carl G P CG   Polasek Ozren O   Pouta Anneli A   Rafelt Suzanne S   Raitakari Olli O   Rayner Nigel W NW   Ridderstråle Martin M   Rief Winfried W   Ruokonen Aimo A   Robertson Neil R NR   Rzehak Peter P   Salomaa Veikko V   Sanders Alan R AR   Sandhu Manjinder S MS   Sanna Serena S   Saramies Jouko J   Savolainen Markku J MJ   Scherag Susann S   Schipf Sabine S   Schreiber Stefan S   Schunkert Heribert H   Silander Kaisa K   Sinisalo Juha J   Siscovick David S DS   Smit Jan H JH   Soranzo Nicole N   Sovio Ulla U   Stephens Jonathan J   Surakka Ida I   Swift Amy J AJ   Tammesoo Mari-Liis ML   Tardif Jean-Claude JC   Teder-Laving Maris M   Teslovich Tanya M TM   Thompson John R JR   Thomson Brian B   Tönjes Anke A   Tuomi Tiinamaija T   van Meurs Joyce B J JB   van Ommen Gert-Jan GJ   Vatin Vincent V   Viikari Jorma J   Visvikis-Siest Sophie S   Vitart Veronique V   Vogel Carla I G CI   Voight Benjamin F BF   Waite Lindsay L LL   Wallaschofski Henri H   Walters G Bragi GB   Widen Elisabeth E   Wiegand Susanna S   Wild Sarah H SH   Willemsen Gonneke G   Witte Daniel R DR   Witteman Jacqueline C JC   Xu Jianfeng J   Zhang Qunyuan Q   Zgaga Lina L   Ziegler Andreas A   Zitting Paavo P   Beilby John P JP   Farooqi I Sadaf IS   Hebebrand Johannes J   Huikuri Heikki V HV   James Alan L AL   Kähönen Mika M   Levinson Douglas F DF   Macciardi Fabio F   Nieminen Markku S MS   Ohlsson Claes C   Palmer Lyle J LJ   Ridker Paul M PM   Stumvoll Michael M   Beckmann Jacques S JS   Boeing Heiner H   Boerwinkle Eric E   Boomsma Dorret I DI   Caulfield Mark J MJ   Chanock Stephen J SJ   Collins Francis S FS   Cupples L Adrienne LA   Smith George Davey GD   Erdmann Jeanette J   Froguel Philippe P   Grönberg Henrik H   Gyllensten Ulf U   Hall Per P   Hansen Torben T   Harris Tamara B TB   Hattersley Andrew T AT   Hayes Richard B RB   Heinrich Joachim J   Hu Frank B FB   Hveem Kristian K   Illig Thomas T   Jarvelin Marjo-Riitta MR   Kaprio Jaakko J   Karpe Fredrik F   Khaw Kay-Tee KT   Kiemeney Lambertus A LA   Krude Heiko H   Laakso Markku M   Lawlor Debbie A DA   Metspalu Andres A   Munroe Patricia B PB   Ouwehand Willem H WH   Pedersen Oluf O   Penninx Brenda W BW   Peters Annette A   Pramstaller Peter P PP   Quertermous Thomas T   Reinehr Thomas T   Rissanen Aila A   Rudan Igor I   Samani Nilesh J NJ   Schwarz Peter E H PE   Shuldiner Alan R AR   Spector Timothy D TD   Tuomilehto Jaakko J   Uda Manuela M   Uitterlinden André A   Valle Timo T TT   Wabitsch Martin M   Waeber Gérard G   Wareham Nicholas J NJ   Watkins Hugh H   Wilson James F JF   Wright Alan F AF   Zillikens M Carola MC   Chatterjee Nilanjan N   McCarroll Steven A SA   Purcell Shaun S   Schadt Eric E EE   Visscher Peter M PM   Assimes Themistocles L TL   Borecki Ingrid B IB   Deloukas Panos P   Fox Caroline S CS   Groop Leif C LC   Haritunians Talin T   Hunter David J DJ   Kaplan Robert C RC   Mohlke Karen L KL   O'Connell Jeffrey R JR   Peltonen Leena L   Schlessinger David D   Strachan David P DP   van Duijn Cornelia M CM   Wichmann H-Erich HE   Frayling Timothy M TM   Thorsteinsdottir Unnur U   Abecasis Gonçalo R GR   Barroso Inês I   Boehnke Michael M   Stefansson Kari K   North Kari E KE   McCarthy Mark I MI   Hirschhorn Joel N JN   Ingelsson Erik E   Loos Ruth J F RJ  

Nature genetics 20101010 11

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy numbe  ...[more]

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