期刊
DIABETOLOGIA
卷 55, 期 4, 页码 981-995出版社
SPRINGER
DOI: 10.1007/s00125-011-2370-7
关键词
Asians; FTO; Meta-analysis; Obesity; Type 2 diabetes
资金
- Hong Kong Government Research Grants Council [CUHK 1/04C]
- Research Grants Council [CUHK4724/07M]
- Government of the Hong Kong SAR [ITS/487/09FP]
- National Institutes of Health [DK078150, TW05596, HL085144, TW008288, R01 AR050496, R21 AG027110, R01 AG026564, R01 AR057049-01A1, R21 AA015973, NIH/FIC KO1 TW006087, NIH/NIDDK R01 DK082766]
- Specialized Center of Research [P50 AR055081]
- National Science Foundation of China [81000363, 31000554]
- PhD Programs Foundation of Ministry of Education of China [20100201120058]
- Fundamental Research Funds for the Central Universities
- Shanghai Leading Academic Discipline Project [S30501]
- National Research Foundation of Korea (NRF) [20100020617]
- Japanese Society for the Promotion of Science [17209021]
- Priority Area 'Applied Genomics' [1601223, 17019028, 18018020, 20018026]
- Korean Ministry of Health Welfare [00-PJ3-PG6-GN07-001]
- National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust
- British Heart Foundation [SP/04/002]
- Medical Research Council [G0700931]
- Wellcome Trust [084723/Z/08/Z]
- National Institute for Health Research [RP-PG-040710371]
- Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [2009KIP401, SIBS2008006]
- Chinese Academy of Sciences [KSCX1-YW-02]
- National Natural Science Foundation of China [30930081]
- National High Technology Research and Development Program (863 Program) [2009AA022704]
- National 973 Program [2011CB504002]
- National Science Council (NSC) of Taiwan [95-3112-B002-002, NSC 96-2752-B002-008-PAE]
- Shanghai Municipality for Basic Research [08dj1400601]
- Program for the National Natural Science Foundation of China [NSFC-30872116]
- New Century Excellent Talents in the University of China [NCET-04-0707]
- Council of Scientific and Industrial Research, Government of India [NWP0032]
- National Heart, Lung, and Blood Institute, National Institutes of Health
- US Department of Health and Human Services [N01WH22110, 24152, 321002, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]
- National Institute of Diabetes and Digestive and Kidney Diseases from National Institutes of Health [DK062290]
- [RR20649]
- [ES10126]
- [DK56350]
- Medical Research Council [G0400519, G0700931, MR/J000094/1, MC_U106188470, G0801056B, G0601966, MC_UP_A620_1016] Funding Source: researchfish
- MRC [G0700931, MC_UP_A620_1016, G0601966, G0400519, MR/J000094/1, MC_U106188470] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [24591347, 21390209, 24591346, 23390247, 17209021] Funding Source: KAKEN
FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 x 10(-19)), overweight by 1.13-fold/allele (p = 1.0 x 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 x 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 x 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 x 10(-17)), WHR by 0.003/allele (p = 1.2 x 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
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