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Meta-Analysis
. 2011 Jun 8:9:71.
doi: 10.1186/1741-7015-9-71.

FTO gene polymorphisms and obesity risk: a meta-analysis

Sihua Peng  1 , Yimin Zhu, Fangying Xu, Xiaobin Ren, Xiaobo Li, Maode Lai
Affiliations
Meta-Analysis

FTO gene polymorphisms and obesity risk: a meta-analysis

Sihua Peng et al. BMC Med. .

Abstract

Background: The pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity-associated gene (FTO); however, as the number of reports increases, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each ethnic group. In addition, some reports have claimed ethnic-specific associations with alternative SNPs, and to that end there has been a degree of confusion.

Methods: We searched PubMed, MEDLINE, Web of Science, EMBASE, and BIOSIS Preview to identify studies investigating the associations between the five polymorphisms and obesity risk. Individual study odds ratios (OR) and their 95% confidence intervals (CI) were estimated using per-allele comparison. Summary ORs were estimated using a random effects model.

Results: We identified 59 eligible case-control studies in 27 articles, investigating 41,734 obesity cases and 69,837 healthy controls. Significant associations were detected between obesity risk and the five polymorphisms: rs9939609 (OR: 1.31, 95% CI: 1.26 to 1.36), rs1421085 (OR: 1.43, 95% CI: 1.33 to 1.53), rs8050136 (OR: 1.25, 95% CI: 1.13 to 1.38), rs17817449 (OR: 1.54, 95% CI: 1.41 to 1.68), and rs1121980 (OR: 1.34, 95% CI: 1.10 to 1.62). Begg's and Egger's tests provided no evidence of publication bias for the polymorphisms except rs1121980. There is evidence of higher heterogeneity, with I2 test values ranging from 38.1% to 84.5%.

Conclusions: This meta-analysis suggests that FTO may represent a low-penetrance susceptible gene for obesity risk. Individual studies with large sample size are needed to further evaluate the associations between the polymorphisms and obesity risk in various ethnic populations.

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Figures

Figure 1
Figure 1
Flow diagram of the study selection for the meta-analyses.
Figure 2
Figure 2
Forest plot of the association between obesity and the rs9939609 polymorphism under per-allele comparison. On the left, the name of the first author of the study is followed by the publication year in parentheses. The size of the black box corresponding to each study is proportional to the sample size, and the horizontal line shows the corresponding 95% CI of the odds ratio (OR). The overall ORs are based on a random-effects model shown by the diamonds. The solid, vertical line represents the null result.
Figure 3
Figure 3
Forest plot of the association between obesity and the two SNPs under per-allele comparison. On the left, the name of the first author of the study is followed by the publication year in parentheses. The size of the black box corresponding to each study is proportional to the sample size, and the horizontal line shows the corresponding 95% CI of the odds ratio (OR). The overall ORs are based on a random-effects model shown by the diamonds. The solid, vertical line represents the null result. (A) rs1421085; (B) rs8050136.
Figure 4
Figure 4
Forest plot of the association between obesity and the two SNPs under per-allele comparison. On the left, the name of the first author of the study is followed by the publication year in parentheses. The size of the black box corresponding to each study is proportional to the sample size, and the horizontal line shows the corresponding 95% CI of the odds ratio (OR). The overall ORs are based on a random-effects model shown by the diamonds. The solid, vertical line represents the null result. (A) rs17917449; (B) rs1121980.
Figure 5
Figure 5
LD pattern of the five SNPs obtained from HapMap database ASW. African ancestry in Southwest USA; CEU, Utah residents with Northern and Western European ancestry from the CEPH collection; CHB, Han Chinese in Beijing, China; CHD, Chinese in Metropolitan Denver, Colorado; GIH, Gujarati Indians in Houston, Texas; JPT, Japanese in Tokyo, Japan; LWK, Luhya in Webuye, Kenya; MEX, Mexican ancestry in Los Angeles, California; MKK, Maasai in Kinyawa, Kenya; TSI, Tuscan in Italy; YRI, Yoruban in Ibadan, Nigeria.
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