A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference.
METHODS
We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m(2)) and waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC.


RESULTS
We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation.


CONCLUSIONS
We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.
Heo
M
M
New York Obesity Research Center, St Luke's-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Leibel
R L
RL
Fontaine
K R
KR
Boyer
B B
BB
Chung
W K
WK
Koulu
M
M
Karvonen
M K
MK
Pesonen
U
U
Rissanen
A
A
Laakso
M
M
Uusitupa
M I J
MI
Chagnon
Y
Y
Bouchard
C
C
Donohoue
P A
PA
Burns
T L
TL
Shuldiner
A R
AR
Silver
K
K
Andersen
R E
RE
Pedersen
O
O
Echwald
S
S
Sørensen
T I A
TI
Behn
P
P
Permutt
M A
MA
Jacobs
K B
KB
Elston
R C
RC
Hoffman
D J
DJ
Gropp
E
E
Allison
D B
DB
D000483:Alleles; D001824:Body Constitution / Q000235:genetics*; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012044:Regression Analysis
D002352:Carrier Proteins; C515448:LEPR protein, human; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin