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

Locke, Adam E ; Kahali, Bratati ; Berndt, Sonja I ; Justice, Anne E ; Pers, Tune H ; Day, Felix R ; Powell, Corey ; Vedantam, Sailaja ; Buchkovich, Martin L and Yang, Jian , et al. (2015) In Nature 518(7538). p.197-401
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
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
in
Nature
volume
518
issue
7538
pages
197 - 401
publisher
Nature Publishing Group
external identifiers
  • pmid:25673413
  • wos:000349190300031
  • scopus:84923171580
ISSN
0028-0836
DOI
10.1038/nature14177
language
English
LU publication?
yes
id
d86b0162-3e09-4c95-b2a6-dc3f755cdec8 (old id 5143923)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract
date added to LUP
2016-04-01 10:48:19
date last changed
2022-04-28 01:17:50
@article{d86b0162-3e09-4c95-b2a6-dc3f755cdec8,
  abstract     = {{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 &lt; 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 &gt;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.}},
  author       = {{Locke, Adam E and Kahali, Bratati and Berndt, Sonja I and Justice, Anne E and Pers, Tune H and Day, Felix R and Powell, Corey and Vedantam, Sailaja and Buchkovich, Martin L and Yang, Jian and Croteau-Chonka, Damien C and Esko, Tonu and Fall, Tove and Ferreira, Teresa and Gustafsson, Stefan and Kutalik, Zoltán and Luan, Jian'an and Mägi, Reedik and Randall, Joshua C and Winkler, Thomas W and Wood, Andrew R and Workalemahu, Tsegaselassie and Faul, Jessica D and Smith, Jennifer A and Hua Zhao, Jing and Zhao, Wei and Chen, Jin and Fehrmann, Rudolf and Hedman, Åsa K and Karjalainen, Juha and Schmidt, Ellen M and Absher, Devin and Amin, Najaf and Anderson, Denise and Beekman, Marian and Bolton, Jennifer L and Bragg-Gresham, Jennifer L and Buyske, Steven and Demirkan, Ayse and Deng, Guohong and Ehret, Georg B and Feenstra, Bjarke and Feitosa, Mary F and Fischer, Krista and Goel, Anuj and Gong, Jian and Jackson, Anne U and Kanoni, Stavroula and Kleber, Marcus E and Kristiansson, Kati and Lim, Unhee and Lotay, Vaneet and Mangino, Massimo and Mateo Leach, Irene and Medina-Gomez, Carolina and Medland, Sarah E and Nalls, Michael A and Palmer, Cameron D and Pasko, Dorota and Pechlivanis, Sonali and Peters, Marjolein J and Prokopenko, Inga and Shungin, Dmitry and Stančáková, Alena and Strawbridge, Rona J and Ju Sung, Yun and Tanaka, Toshiko and Teumer, Alexander and Trompet, Stella and van der Laan, Sander W and van Setten, Jessica and Van Vliet-Ostaptchouk, Jana V and Wang, Zhaoming and Yengo, Loïc and Zhang, Weihua and Isaacs, Aaron and Albrecht, Eva and Ärnlöv, Johan and Arscott, Gillian M and Attwood, Antony P and Bandinelli, Stefania and Barrett, Amy and Bas, Isabelita N and Bellis, Claire and Bennett, Amanda J and Berne, Christian and Blagieva, Roza and Blüher, Matthias and Böhringer, Stefan and Bonnycastle, Lori L and Böttcher, Yvonne and Boyd, Heather A and Bruinenberg, Marcel and Caspersen, Ida H and Ida Chen, Yii-Der and Clarke, Robert and 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Kathleen and Stringham, Heather M and Sundström, Johan and Swertz, Morris A and Swift, Amy J and Syvänen, Ann-Christine and Tan, Sian-Tsung and Tayo, Bamidele O and Thorand, Barbara and Thorleifsson, Gudmar and Tyrer, Jonathan P and Uh, Hae-Won and Vandenput, Liesbeth and Verhulst, Frank C and Vermeulen, Sita H and Verweij, Niek and Vonk, Judith M and Waite, Lindsay L and Warren, Helen R and Waterworth, Dawn and Weedon, Michael N and Wilkens, Lynne R and Willenborg, Christina and Wilsgaard, Tom and Wojczynski, Mary K and Wong, Andrew and Wright, Alan F and Zhang, Qunyuan and Brennan, Eoin P and Choi, Murim and Dastani, Zari and Drong, Alexander W and Eriksson, Per and Franco-Cereceda, Anders and Gådin, Jesper R and Gharavi, Ali G and Goddard, Michael E and Handsaker, Robert E and Huang, Jinyan and Karpe, Fredrik and Kathiresan, Sekar and Keildson, Sarah and Kiryluk, Krzysztof and Kubo, Michiaki and Lee, Jong-Young and Liang, Liming and Lifton, Richard P and Ma, Baoshan and McCarroll, Steven A and McKnight, Amy J and Min, Josine L and Moffatt, Miriam F and Montgomery, Grant W and Murabito, Joanne M and Nicholson, George and Nyholt, Dale R and Okada, Yukinori and Perry, John R B and Dorajoo, Rajkumar and Reinmaa, Eva and Salem, Rany M and Sandholm, Niina and Scott, Robert A and Stolk, Lisette and Takahashi, Atsushi and Tanaka, Toshihiro and Van't Hooft, Ferdinand M and Vinkhuyzen, Anna A E and Westra, Harm-Jan and Zheng, Wei and Zondervan, Krina T and Heath, Andrew C and Arveiler, Dominique and Bakker, Stephan J L and Beilby, John and Bergman, Richard N and Blangero, John and Bovet, Pascal and Campbell, Harry and Caulfield, Mark J and Cesana, Giancarlo and Chakravarti, Aravinda and Chasman, Daniel I and Chines, Peter S and Collins, Francis S and Crawford, Dana C and Cupples, L Adrienne and Cusi, Daniele and Danesh, John and de Faire, Ulf and den Ruijter, Hester M and Dominiczak, Anna F and Erbel, Raimund and Erdmann, Jeanette and Eriksson, Johan G and Farrall, Martin 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Erik and Hirschhorn, Joel N and Loos, Ruth J F and Speliotes, Elizabeth K}},
  issn         = {{0028-0836}},
  keywords     = {{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}},
  language     = {{eng}},
  number       = {{7538}},
  pages        = {{197--401}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature}},
  title        = {{Genetic studies of body mass index yield new insights for obesity biology.}},
  url          = {{http://dx.doi.org/10.1038/nature14177}},
  doi          = {{10.1038/nature14177}},
  volume       = {{518}},
  year         = {{2015}},
}