Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals.
OBJECTIVE
Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women.


METHODS
We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 x 10(-4) for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin.


RESULTS
The ADIPOQ locus showed genome-wide significant p-values in the combined (p=4.3 x 10(-24)) as well as in both women- and men-specific analyses (p=8.7 x 10(-17) and p=2.5 x 10(-11), respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci exhibited association with plasma adiponectin (p>0.01).


CONCLUSIONS
We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which explains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci explained the sex differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin.
Heid
Iris M
IM
Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany.
Henneman
Peter
P
Hicks
Andrew
A
Coassin
Stefan
S
Winkler
Thomas
T
Aulchenko
Yurii S
YS
Fuchsberger
Christian
C
Song
Kijoung
K
Hivert
Marie-France
MF
Waterworth
Dawn M
DM
Timpson
Nicholas J
NJ
Richards
J Brent
JB
Perry
John R B
JR
Tanaka
Toshiko
T
Amin
Najaf
N
Kollerits
Barbara
B
Pichler
Irene
I
Oostra
Ben A
BA
Thorand
Barbara
B
Frants
Rune R
RR
Illig
Thomas
T
Dupuis
Josée
J
Glaser
Beate
B
Spector
Tim
T
Guralnik
Jack
J
Egan
Josephine M
JM
Florez
Jose C
JC
Evans
David M
DM
Soranzo
Nicole
N
Bandinelli
Stefania
S
Carlson
Olga D
OD
Frayling
Timothy M
TM
Burling
Keith
K
Smith
George Davey
GD
Mooser
Vincent
V
Ferrucci
Luigi
L
Meigs
James B
JB
Vollenweider
Peter
P
Dijk
Ko Willems van
KW
Pramstaller
Peter
P
Kronenberg
Florian
F
van Duijn
Cornelia M
CM
D052242:Adiponectin / Q000097:blood; D002318:Cardiovascular Diseases / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D005060:Europe; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
C499918:ADIPOQ protein, human; D052242:Adiponectin