Associations of genetic variants in/near body mass index‐associated genes with type 2 diabetes: a systematic meta‐analysis. (13th March 2014)

• Record Type: Journal Article
• 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.; DIAGRAM Consortium; AGEN‐T2D Consortium; SAT2D Consortium
• Is Part Of: Clinical endocrinology. Volume 81:Number 5(2014:Nov.)
• Page Start: 702
• Page End: 710
• Publication Date: 2014-03-13
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12428
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12428-abs-0001"> <title>Summary</title> <sec id="cen12428-sec-0001" sec-type="section"> <title>Objective</title> <p>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 (T2D). However, the results have been inconsistent. The objective of this study was to investigate the associations of eleven obesity/BMI loci with T2D risk and explore how BMI influences this risk.</p> </sec> <sec id="cen12428-sec-0002" sec-type="section"> <title>Methods</title> <p>We retrieved published literature from PubMed and Embase. The pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using fixed‐ or random‐effect models.</p> </sec> <sec id="cen12428-sec-0003" sec-type="section"> <title>Results</title> <p>In the meta‐analysis of 42 studies for 11 obesity/BMI‐associated loci, we observed a statistically significant association of the <italic>FTO</italic> rs9939609 polymorphism (66 425 T2D cases/239 689 normoglycaemic subjects; <italic>P </italic>=<italic> </italic>1·00 × 10<sup>−41</sup>) and six other variants with T2D risk (17 915 T2D cases/27 531 normoglycaemic individuals: <italic>n</italic> = 40 629–130 001; all <italic>P </italic><<italic> </italic>0·001 for <italic>SH2B1</italic> rs7498665, <italic>FAIM2</italic> rs7138803, <italic>TMEM18</italic> rs7561317, <italic>GNPDA2</italic> rs10938397, <italic>BDNF</italic> rs925946 and <italic>NEGR1</italic> rs2568958). After adjustment for BMI, the association remained statistically significant for four of the seven variants (all <italic>P </italic><<italic> </italic>0·05 for <italic>FTO</italic> rs9939609, <italic>SH2B1</italic> rs7498665, <italic>FAIM2</italic> rs7138803, <italic>GNPDA2</italic> rs10938397). Subgroup analysis by ethnicity demonstrated similar results.</p> </sec> <sec id="cen12428-sec-0004" sec-type="section"> <title>Conclusions</title> <p>This meta‐analysis indicates that several BMI‐associated variants are significantly associated with T2D risk. Some variants increase the T2D risk independent of obesity, while others mediate this risk through obesity.</p> </sec> </abstract>