Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
Lindgren
Cecilia M
CM
Wellcome Trust Centre for Human Genetics, University of Oxford, , Oxford, United Kingdom.
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Iris M
IM
Randall
Joshua C
JC
Lamina
Claudia
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Steinthorsdottir
Valgerdur
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Qi
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Speliotes
Elizabeth K
EK
Thorleifsson
Gudmar
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BM
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Anne U
AU
Lim
Noha
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Paul
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John C
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Lori L
LL
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L
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P
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Alex S F
AS
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Paul
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Michael R
MR
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Karol
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Ferrucci
Luigi
L
Fischer
Guido
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Nita G
NG
Gieger
Christian
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Grallert
Harald
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Christopher J
CJ
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Guiducci
Candace
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Havulinna
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Rolf
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John W
JW
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Isomaa
Bo
B
Jacobs
Leonie C
LC
Jameson
Karen
K
Jousilahti
Pekka
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Karpe
Fredrik
F
Kuusisto
Johanna
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Laitinen
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Lathrop
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GM
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Debbie A
DA
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WL
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T
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Mario A
MA
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AP
Munroe
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Narisu
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N
Nordström
Anna
A
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Ben A
BA
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CN
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Felicity
F
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John F
JF
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Inga
I
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Frida
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Aimo
A
Salomaa
Veikko
V
Sandhu
Manjinder S
MS
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Laura J
LJ
Scuteri
Angelo
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Silander
Kaisa
K
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Kijoung
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Yuan
Xin
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Stringham
Heather M
HM
Swift
Amy J
AJ
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Tiinamaija
T
Uda
Manuela
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Vollenweider
Peter
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G Bragi
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Jacqueline C M
JC
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Cuilin
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Weihua
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MJ
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Francis S
FS
Davey Smith
George
G
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Ian N M
IN
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Paul W
PW
Hattersley
Andrew T
AT
Hu
Frank B
FB
Jarvelin
Marjo-Riitta
MR
Kong
Augustine
A
Kooner
Jaspal S
JS
Laakso
Markku
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E
Mooser
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Andrew D
AD
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Timothy D
TD
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DP
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T
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AG
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CM
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DM
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M
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L
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DJ
Thorsteinsdottir
Unnur
U
Schlessinger
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D
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H-Erich
HE
Frayling
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TM
Abecasis
Gonçalo R
GR
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Joel N
JN
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Ruth J F
RJ
Stefansson
Kari
K
Mohlke
Karen L
KL
Barroso
Inês
I
McCarthy
Mark I
MI
D050154:Adiposity; D000328:Adult; D050218:Body Fat Distribution; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008245:Lysophospholipase / Q000235:genetics*; D008297:Male; D051150:Methionine Sulfoxide Reductases; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D050656:Transcription Factor AP-2 / Q000235:genetics*; D055105:Waist Circumference; D049629:Waist-Hip Ratio
C493677:TFAP2B protein, human; D050656:Transcription Factor AP-2; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D008245:Lysophospholipase