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- Title
Associations of genetic variants in/near body mass index-associated genes with type 2 diabetes: a systematic meta-analysis.
- Authors
Xi, Bo; Takeuchi, Fumihiko; Meirhaeghe, Aline; Kato, Norihiro; Chambers, John C.; Morris, Andrew P.; Cho, Yoon Shin; Zhang, Weihua; Mohlke, Karen L.; Kooner, Jaspal S.; Shu, Xiao Ou; Pan, Hongwei; Tai, E Shyong; Pan, Haiyan; Wu, Jer‐Yuarn; Zhou, Donghao; Chandak, Giriraj R.
- Abstract
Objective Genome-wide association studies have identified many obesity/body mass index ( BMI)-associated loci in Europeans and East Asians. Since then, a large number of studies have investigated the role of BMI-associated loci in the development of type 2 diabetes ( T2 D). However, the results have been inconsistent. The objective of this study was to investigate the associations of eleven obesity/ BMI loci with T2 D risk and explore how BMI influences this risk. Methods We retrieved published literature from Pub Med and Embase. The pooled odds ratios ( OR) with 95% confidence intervals ( CI) were calculated using fixed- or random-effect models. Results In the meta-analysis of 42 studies for 11 obesity/ BMI-associated loci, we observed a statistically significant association of the FTO rs9939609 polymorphism (66 425 T2 D cases/239 689 normoglycaemic subjects; P = 1·00 × 10−41) and six other variants with T2 D risk (17 915 T2 D cases/27 531 normoglycaemic individuals: n = 40 629-130 001; all P < 0·001 for SH2B1 rs7498665, FAIM2 rs7138803, TMEM18 rs7561317, GNPDA2 rs10938397, BDNF rs925946 and NEGR1 rs2568958). After adjustment for BMI, the association remained statistically significant for four of the seven variants (all P < 0·05 for FTO rs9939609, SH2B1 rs7498665, FAIM2 rs7138803, GNPDA2 rs10938397). Subgroup analysis by ethnicity demonstrated similar results. Conclusions This meta-analysis indicates that several BMI-associated variants are significantly associated with T2 D risk. Some variants increase the T2 D risk independent of obesity, while others mediate this risk through obesity.
- Subjects
GENETIC correlations; GENETIC research; BODY mass index; TYPE 2 diabetes; META-analysis
- Publication
Clinical Endocrinology, 2014, Vol 81, Issue 5, p702
- ISSN
0300-0664
- Publication type
Article
- DOI
10.1111/cen.12428