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

GIANT Consortium

doi:10.1038/ng.287

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

GIANT Consortium

University of Michigan, Ann Arbor
Massachusetts General Hospital
Massachusetts Institute of Technology
Addenbrooke's Hospital
University of Oxford
German Research Center for Environmental Health
National Cancer Institute (Bethesda, Md)
Broad Institute of MIT and Harvard
Boston Children's Hospital and Harvard Medical School
Medical Genetics/Clinical Pharmacology and Discovery Medicine
City St George's, University of London
Harvard T.H. Chan School of Public Health
Harvard Medical School
Wellcome Sanger Institute
Institute of Legal Informatics and Judicial Systems (IGSiG-CNR)
Peninsula Medical School, Universities of Exeter and Plymouth
King's College London
National Institutes of Health
University of Bristol
Lund University
Oxford University Hospitals NHS Foundation Trust
Keck School of Medicine of USC
Wellcome Trust
University of Cambridge
National Human Genome Research Institute (NHGRI)
Imperial College London
Glasgow Cardiovascular Research Centre
MRC Lifecourse Epidemiology Unit

Research output: Contribution to journal › Article › Academic › peer-review

1511 Citations (Scopus)

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.

Original language	English
Pages (from-to)	25-34
Number of pages	10
Journal	Nature Genetics
Volume	41
Issue number	1
DOIs	https://doi.org/10.1038/ng.287
Publication status	Published - Jan 2009

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10.1038/ng.287

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@article{91464ef9c56e40e2bf5f5da7f3b2eadf,

title = "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation",

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 {\texttimes} 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.",

author = "Willer, \{Cristen J.\} and Speliotes, \{Elizabeth K.\} and \{GIANT Consortium\} and Loos, \{Ruth J.F.\} and Shengxu Li and Lindgren, \{Cecilia M.\} and Heid, \{Iris M.\} and Berndt, \{Sonja I.\} and Elliott, \{Amanda L.\} and Jackson, \{Anne U.\} and Claudia Lamina and Guillaume Lettre and Noha Lim and Lyon, \{Helen N.\} and McCarroll, \{Steven A.\} and Konstantinos Papadakis and Lu Qi and Randall, \{Joshua C.\} and Roccasecca, \{Rosa Maria\} and Serena Sanna and Paul Scheet and Weedon, \{Michael N.\} and Eleanor Wheeler and Zhao, \{Jing Hua\} and Jacobs, \{Leonie C.\} and Inga Prokopenko and Nicole Soranzo and Toshiko Tanaka and Timpson, \{Nicholas J.\} and Peter Almgren and Amanda Bennett and Bergman, \{Richard N.\} and Bingham, \{Sheila A.\} and Bonnycastle, \{Lori L.\} and Morris Brown and Burtt, \{No{\"e}l P.\} and Peter Chines and Lachlan Coin and Collins, \{Francis S.\} and Connell, \{John M.\} and Cyrus Cooper and Smith, \{George Davey\} and Dennison, \{Elaine M.\} and Parimal Deodhar and Paul Elliott and Albert Hofman and Peter Kraft and Fernando Rivadeneira and \{Van Duijn\}, \{Cornelia M.\} and Zillikens, \{M. Carola\} and Uitterlinden, \{Andr{\'e} G.\}",

year = "2009",

month = jan,

doi = "10.1038/ng.287",

language = "English",

volume = "41",

pages = "25--34",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "1",

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TY - JOUR

T1 - Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

AU - Willer, Cristen J.

AU - Speliotes, Elizabeth K.

AU - GIANT Consortium

AU - Loos, Ruth J.F.

AU - Li, Shengxu

AU - Lindgren, Cecilia M.

AU - Heid, Iris M.

AU - Berndt, Sonja I.

AU - Elliott, Amanda L.

AU - Jackson, Anne U.

AU - Lamina, Claudia

AU - Lettre, Guillaume

AU - Lim, Noha

AU - Lyon, Helen N.

AU - McCarroll, Steven A.

AU - Papadakis, Konstantinos

AU - Qi, Lu

AU - Randall, Joshua C.

AU - Roccasecca, Rosa Maria

AU - Sanna, Serena

AU - Scheet, Paul

AU - Weedon, Michael N.

AU - Wheeler, Eleanor

AU - Zhao, Jing Hua

AU - Jacobs, Leonie C.

AU - Prokopenko, Inga

AU - Soranzo, Nicole

AU - Tanaka, Toshiko

AU - Timpson, Nicholas J.

AU - Almgren, Peter

AU - Bennett, Amanda

AU - Bergman, Richard N.

AU - Bingham, Sheila A.

AU - Bonnycastle, Lori L.

AU - Brown, Morris

AU - Burtt, Noël P.

AU - Chines, Peter

AU - Coin, Lachlan

AU - Collins, Francis S.

AU - Connell, John M.

AU - Cooper, Cyrus

AU - Smith, George Davey

AU - Dennison, Elaine M.

AU - Deodhar, Parimal

AU - Elliott, Paul

AU - Hofman, Albert

AU - Kraft, Peter

AU - Rivadeneira, Fernando

AU - Van Duijn, Cornelia M.

AU - Zillikens, M. Carola

AU - Uitterlinden, André G.

PY - 2009/1

Y1 - 2009/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/58149163142

U2 - 10.1038/ng.287

DO - 10.1038/ng.287

M3 - Article

C2 - 19079261

AN - SCOPUS:58149163142

SN - 1061-4036

VL - 41

SP - 25

EP - 34

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

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

Abstract

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