Meta-analysis of genome-wide linkage studies in BMI and obesity.
OBJECTIVE
The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis.


METHODS
We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry.


RESULTS
Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01).


CONCLUSIONS
Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.
Saunders
Catherine L
CL
King's College London, Guy's, King's & St. Thomas' School of Medicine, London, United Kingdom.
Chiodini
Benedetta D
BD
Sham
Pak
P
Lewis
Cathryn M
CM
Abkevich
Victor
V
Adeyemo
Adebowale A
AA
de Andrade
Mariza
M
Arya
Rector
R
Berenson
Gerald S
GS
Blangero
John
J
Boehnke
Michael
M
Borecki
Ingrid B
IB
Chagnon
Yvon C
YC
Chen
Wei
W
Comuzzie
Anthony G
AG
Deng
Hong-Wen
HW
Duggirala
Ravindranath
R
Feitosa
Mary F
MF
Froguel
Philippe
P
Hanson
Robert L
RL
Hebebrand
Johannes
J
Huezo-Dias
Patricia
P
Kissebah
Ahmed H
AH
Li
Weidong
W
Luke
Amy
A
Martin
Lisa J
LJ
Nash
Matthew
M
Ohman
Miina
M
Palmer
Lyle J
LJ
Peltonen
Leena
L
Perola
Markus
M
Price
R Arlen
RA
Redline
Susan
S
Srinivasan
Sathanur R
SR
Stern
Michael P
MP
Stone
Steven
S
Stringham
Heather
H
Turner
Stephen
S
Wijmenga
Cisca
C
Collier
David A
DA
D050154:Adiposity; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000235:genetics; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D006973:Hypertension / Q000235:genetics; D009765:Obesity / Q000235:genetics*