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 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.
Willer
Cristen J
CJ
Genetic Investigation of ANthropometric Traits Consortium.
Speliotes
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EK
Loos
Ruth J F
RJ
Li
Shengxu
S
Lindgren
Cecilia M
CM
Heid
Iris M
IM
Berndt
Sonja I
SI
Elliott
Amanda L
AL
Jackson
Anne U
AU
Lamina
Claudia
C
Lettre
Guillaume
G
Lim
Noha
N
Lyon
Helen N
HN
McCarroll
Steven A
SA
Papadakis
Konstantinos
K
Qi
Lu
L
Randall
Joshua C
JC
Roccasecca
Rosa Maria
RM
Sanna
Serena
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Scheet
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P
Weedon
Michael N
MN
Wheeler
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Zhao
Jing Hua
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Jacobs
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Prokopenko
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Soranzo
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Parimal
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Evans
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Guiducci
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Hebebrand
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Hofman
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Khaw
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Kuusisto
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Laitinen
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Jian'an
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McArdle
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WL
Meitinger
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Mulas
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PB
Narisu
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Northstone
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O'Rahilly
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Purmann
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MG
Ridderstråle
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SM
Rivadeneira
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Ruokonen
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LJ
Scuteri
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MA
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Valle
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Vollenweider
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Waeber
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Jacqueline C M
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Guangju
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Zillikens
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Altshuler
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Chanock
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Farooqi
I Sadaf
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Ferrucci
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Guralnik
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Hattersley
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Jarvelin
Marjo-Riitta
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Laakso
Markku
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Abecasis
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D000483:Alleles; D000886:Anthropometry; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D002490:Central Nervous System / Q000502:physiology*; D015331:Cohort Studies; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015201:Meta-Analysis as Topic; D009765:Obesity / Q000150:complications / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable