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

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

doi:10.1038/ng.287

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

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

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

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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 x 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

Keywords

GENOME-WIDE ASSOCIATION
CORONARY-ARTERY-DISEASE
FTO GENE
ALCOHOL DEPENDENCE
COMMON VARIANTS
NEURITE OUTGROWTH
CHILDHOOD OBESITY
ADULT OBESITY
EXPRESSION
MICE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.287

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Willer, C. J., Speliotes, E. K., Loos, R. J. F., Li, S., Lindgren, C. M., Heid, I. M., Berndt, S. I., Elliott, A. L., Jackson, A. U., Lamina, C., Lettre, G., Lim, N., Lyon, H. N., McCarroll, S. A., Papadakis, K., Qi, L., Randall, J. C., Roccasecca, R. M., Sanna, S., ... Giant Consortium, Wellcome Trust Case Control (2009). Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature Genetics, 41(1), 25-34. https://doi.org/10.1038/ng.287

@article{91d017fb3b2f4cbda99822ecbc779a50,

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 x 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.",

keywords = "GENOME-WIDE ASSOCIATION, CORONARY-ARTERY-DISEASE, FTO GENE, ALCOHOL DEPENDENCE, COMMON VARIANTS, NEURITE OUTGROWTH, CHILDHOOD OBESITY, ADULT OBESITY, EXPRESSION, MICE",

author = "Willer, {Cristen J.} and Speliotes, {Elizabeth K.} 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, {Noel 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 Erdos, {Michael R.} and Karol Estrada and Evans, {David M.} and Lauren Gianniny and Christian Gieger and Gillson, {Christopher J.} and {Giant Consortium, Wellcome Trust Case Control}",

year = "2009",

month = jan,

doi = "10.1038/ng.287",

language = "English",

volume = "41",

pages = "25--34",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "1",

}

Willer, CJ, Speliotes, EK, Loos, RJF, Li, S, Lindgren, CM, Heid, IM, Berndt, SI, Elliott, AL, Jackson, AU, Lamina, C, Lettre, G, Lim, N, Lyon, HN, McCarroll, SA, Papadakis, K, Qi, L, Randall, JC, Roccasecca, RM, Sanna, S, Scheet, P, Weedon, MN, Wheeler, E, Zhao, JH, Jacobs, LC, Prokopenko, I, Soranzo, N, Tanaka, T, Timpson, NJ, Almgren, P, Bennett, A, Bergman, RN, Bingham, SA, Bonnycastle, LL, Brown, M, Burtt, NLP, Chines, P, Coin, L, Collins, FS, Connell, JM, Cooper, C, Smith, GD, Dennison, EM, Deodhar, P, Elliott, P, Erdos, MR, Estrada, K, Evans, DM, Gianniny, L, Gieger, C, Gillson, CJ & Giant Consortium, Wellcome Trust Case Control 2009, 'Six new loci associated with body mass index highlight a neuronal influence on body weight regulation', Nature Genetics, vol. 41, no. 1, pp. 25-34. https://doi.org/10.1038/ng.287

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 - 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, Noel L. 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 - Erdos, Michael R.

AU - Estrada, Karol

AU - Evans, David M.

AU - Gianniny, Lauren

AU - Gieger, Christian

AU - Gillson, Christopher J.

AU - Giant Consortium, Wellcome Trust Case Control

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 x 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 x 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.

KW - GENOME-WIDE ASSOCIATION

KW - CORONARY-ARTERY-DISEASE

KW - FTO GENE

KW - ALCOHOL DEPENDENCE

KW - COMMON VARIANTS

KW - NEURITE OUTGROWTH

KW - CHILDHOOD OBESITY

KW - ADULT OBESITY

KW - EXPRESSION

KW - MICE

U2 - 10.1038/ng.287

DO - 10.1038/ng.287

M3 - Article

C2 - 19079261

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

Keywords

UN SDGs

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