Assessment of genetic linkage and parent-of-origin effects on obesity.
BACKGROUND
Obesity is a growing health care problem worldwide and is a major underlying risk factor for common diseases such as diabetes. Parent-of-origin effect has been reported to be involved in the development of obesity. But the genes with imprinting effects related to obesity are largely unknown.


OBJECTIVE
The objective of the study was to identify obesity-related genetic loci, both with and without imprinting effects.


METHODS
We conducted genome-wide linkage analyses for obesity with and without consideration of imprinting effects in a large sample including more than 4000 individuals. In addition to body mass index (BMI), we also used a more stringent and accurate obesity definition, which simultaneously considers BMI and percentage of fat mass (PFM) in a gender-specific manner. Simulations were performed to identify the genome-wide significant and suggestive significant thresholds.


RESULTS
In nonimprinted linkage analyses, we detected suggestive linkage at 2q31 (LOD = 2.23) and 16q22 (LOD = 1.87) for BMI and 2q37 (LOD = 2.23) for BMI and PFM. Interestingly, 2q37 also achieved a significant maternal linkage with BMI and PFM (LOD=3.34) in imprinted linkage analyses. Imprinted linkage analyses revealed suggestive linkage evidence for BMI at three additional genomic regions, including 3p14 (LOD = 2.20, paternal), 3q24 (LOD = 1.97, maternal), and 19q13 (LOD = 1.81, maternal).


CONCLUSIONS
We reported linkage and imprinting effects for obesity on several chromosome regions and suggested the potential importance of parent-of-origin effects and phenotype definition of obesity in delineating the genetic basis of obesity.
Guo
Yan-Fang
YF
Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiantong University, Xi'an 710049, People's Republic of China.
Shen
Hui
H
Liu
Yong-jun
YJ
Wang
Wei
W
Xiong
Dong-hai
DH
Xiao
Peng
P
Liu
Yao-zhong
YZ
Zhao
Lan-juan
LJ
Recker
Robert R
RR
Deng
Hong-wen
HW
D000273:Adipose Tissue / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D009765:Obesity / Q000235:genetics*; D010290:Parents