A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.
Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.
Frayling
Timothy M
TM
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK.
Timpson
Nicholas J
NJ
Weedon
Michael N
MN
Zeggini
Eleftheria
E
Freathy
Rachel M
RM
Lindgren
Cecilia M
CM
Perry
John R B
JR
Elliott
Katherine S
KS
Lango
Hana
H
Rayner
Nigel W
NW
Shields
Beverley
B
Harries
Lorna W
LW
Barrett
Jeffrey C
JC
Ellard
Sian
S
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CJ
Knight
Bridget
B
Patch
Ann-Marie
AM
Ness
Andrew R
AR
Ebrahim
Shah
S
Lawlor
Debbie A
DA
Ring
Susan M
SM
Ben-Shlomo
Yoav
Y
Jarvelin
Marjo-Riitta
MR
Sovio
Ulla
U
Bennett
Amanda J
AJ
Melzer
David
D
Ferrucci
Luigi
L
Loos
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RJ
Barroso
Inês
I
Wareham
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NJ
Karpe
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F
Owen
Katharine R
KR
Cardon
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LR
Walker
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M
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Graham A
GA
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CN
Doney
Alex S F
AS
Morris
Andrew D
AD
Smith
George Davey
GD
Hattersley
Andrew T
AT
McCarthy
Mark I
MI
D000273:Adipose Tissue; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001724:Birth Weight; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom