Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity.
Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.
Thorleifsson
Gudmar
G
deCODE Genetics, Reykjavik, Iceland. thorleif@decode.is
Walters
G Bragi
GB
Gudbjartsson
Daniel F
DF
Steinthorsdottir
Valgerdur
V
Sulem
Patrick
P
Helgadottir
Anna
A
Styrkarsdottir
Unnur
U
Gretarsdottir
Solveig
S
Thorlacius
Steinunn
S
Jonsdottir
Ingileif
I
Jonsdottir
Thorbjorg
T
Olafsdottir
Elinborg J
EJ
Olafsdottir
Gudridur H
GH
Jonsson
Thorvaldur
T
Jonsson
Frosti
F
Borch-Johnsen
Knut
K
Hansen
Torben
T
Andersen
Gitte
G
Jorgensen
Torben
T
Lauritzen
Torsten
T
Aben
Katja K
KK
Verbeek
André L M
AL
Roeleveld
Nel
N
Kampman
Ellen
E
Yanek
Lisa R
LR
Becker
Lewis C
LC
Tryggvadottir
Laufey
L
Rafnar
Thorunn
T
Becker
Diane M
DM
Gulcher
Jeffrey
J
Kiemeney
Lambertus A
LA
Pedersen
Oluf
O
Kong
Augustine
A
Thorsteinsdottir
Unnur
U
Stefansson
Kari
K
D001483:Base Sequence; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D009765:Obesity / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable