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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 10-8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
1061-4036
25-34
Willer, Cristen J.
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Speliotes, Elizabeth K.
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Loos, Ruth J.F.
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Li, Shengxu
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Lindgren, Cecilia M.
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Heid, Iris M.
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Elliott, Amanda L.
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Jackson, Anne U.
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Lamina, Claudia
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Lettre, Guillaume
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Lim, Noha
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Lyon, Helen N.
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McCarroll, Steven A.
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Papadakis, Konstantinos
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Qi, Lu
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Roccasecca, Rosa Maria
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Almgren, Peter
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Bennett, Amanda
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Bonnycastle, Lori L.
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Brown, Morris
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Burtt, Noël P.
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Chines, Peter
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Coin, Lachlan
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Collins, Francis S.
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Connell, John M.
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Cooper, Cyrus
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Smith, George Davey
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Dennison, Elaine M.
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Deodhar, Parimal
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Elliott, Paul
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Erdos, Michael R.
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Estrada, Karol
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Evans, David M.
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Gianniny, Lauren
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Gieger, Christian
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Gillson, Christopher J.
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GIANT Consortium
Willer, Cristen J.
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Speliotes, Elizabeth K.
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Loos, Ruth J.F.
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Li, Shengxu
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Lindgren, Cecilia M.
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Heid, Iris M.
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Berndt, Sonja I.
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Elliott, Amanda L.
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Jackson, Anne U.
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Lamina, Claudia
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Lettre, Guillaume
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Lim, Noha
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Lyon, Helen N.
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McCarroll, Steven A.
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Papadakis, Konstantinos
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Qi, Lu
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Randall, Joshua C.
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Roccasecca, Rosa Maria
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Sanna, Serena
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Scheet, Paul
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Weedon, Michael N.
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Wheeler, Eleanor
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Zhao, Jing Hua
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Jacobs, Leonie C.
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Prokopenko, Inga
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Soranzo, Nicole
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Tanaka, Toshiko
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Timpson, Nicholas J.
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Almgren, Peter
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Bennett, Amanda
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Bergman, Richard N.
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Bingham, Sheila A.
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Bonnycastle, Lori L.
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Brown, Morris
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Burtt, Noël P.
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Chines, Peter
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Coin, Lachlan
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Collins, Francis S.
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Connell, John M.
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Cooper, Cyrus
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Smith, George Davey
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Dennison, Elaine M.
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Deodhar, Parimal
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Elliott, Paul
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Erdos, Michael R.
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Estrada, Karol
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Evans, David M.
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Gianniny, Lauren
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Gieger, Christian
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Gillson, Christopher J.
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Willer, Cristen J., Speliotes, Elizabeth K., Loos, Ruth J.F., Li, Shengxu, Lindgren, Cecilia M., Heid, Iris M., Berndt, Sonja I., Elliott, Amanda L., Jackson, Anne U., Lamina, Claudia, Lettre, Guillaume, Lim, Noha, Lyon, Helen N., McCarroll, Steven A., Papadakis, Konstantinos, Qi, Lu, Randall, Joshua C., Roccasecca, Rosa Maria, Sanna, Serena, Scheet, Paul, Weedon, Michael N., Wheeler, Eleanor, Zhao, Jing Hua, Jacobs, Leonie C., Prokopenko, Inga, Soranzo, Nicole, Tanaka, Toshiko, Timpson, Nicholas J., Almgren, Peter, Bennett, Amanda, Bergman, Richard N., Bingham, Sheila A., Bonnycastle, Lori L., Brown, Morris, Burtt, Noël P., Chines, Peter, Coin, Lachlan, Collins, Francis S., Connell, John M., Cooper, Cyrus, Smith, George Davey, Dennison, Elaine M., Deodhar, Parimal, Elliott, Paul, Erdos, Michael R., Estrada, Karol, Evans, David M., Gianniny, Lauren, Gieger, Christian and Gillson, Christopher J. , GIANT Consortium (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature Genetics, 41 (1), 25-34. (doi:10.1038/ng.287). (PMID:19079261)

Record type: Article

Abstract

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 10-8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

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More information

e-pub ahead of print date: 14 December 2008
Published date: January 2009
Organisations: Dev Origins of Health & Disease

Identifiers

Local EPrints ID: 341040
URI: http://eprints.soton.ac.uk/id/eprint/341040
DOI: doi:10.1038/ng.287
ISSN: 1061-4036
PURE UUID: cceeb689-687f-40db-bff3-c6ecf4d79df5
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Elaine M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961

Catalogue record

Date deposited: 11 Jul 2012 15:14
Last modified: 18 Mar 2024 02:45

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Contributors

Author: Cristen J. Willer
Author: Elizabeth K. Speliotes
Author: Ruth J.F. Loos
Author: Shengxu Li
Author: Cecilia M. Lindgren
Author: Iris M. Heid
Author: Sonja I. Berndt
Author: Amanda L. Elliott
Author: Anne U. Jackson
Author: Claudia Lamina
Author: Guillaume Lettre
Author: Noha Lim
Author: Helen N. Lyon
Author: Steven A. McCarroll
Author: Konstantinos Papadakis
Author: Lu Qi
Author: Joshua C. Randall
Author: Rosa Maria Roccasecca
Author: Serena Sanna
Author: Paul Scheet
Author: Michael N. Weedon
Author: Eleanor Wheeler
Author: Jing Hua Zhao
Author: Leonie C. Jacobs
Author: Inga Prokopenko
Author: Nicole Soranzo
Author: Toshiko Tanaka
Author: Nicholas J. Timpson
Author: Peter Almgren
Author: Amanda Bennett
Author: Richard N. Bergman
Author: Sheila A. Bingham
Author: Lori L. Bonnycastle
Author: Morris Brown
Author: Noël P. Burtt
Author: Peter Chines
Author: Lachlan Coin
Author: Francis S. Collins
Author: John M. Connell
Author: Cyrus Cooper ORCID iD
Author: George Davey Smith
Author: Elaine M. Dennison ORCID iD
Author: Parimal Deodhar
Author: Paul Elliott
Author: Michael R. Erdos
Author: Karol Estrada
Author: David M. Evans
Author: Lauren Gianniny
Author: Christian Gieger
Author: Christopher J. Gillson
Corporate Author: GIANT Consortium

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