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Diabetologia
Published in: Diabetologia 4/2012

Open Access 01-04-2012 | Article

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians

Authors: H. Li, T. O. Kilpeläinen, C. Liu, J. Zhu, Y. Liu, C. Hu, Z. Yang, W. Zhang, W. Bao, S. Cha, Y. Wu, T. Yang, A. Sekine, B. Y. Choi, C. S. Yajnik, D. Zhou, F. Takeuchi, K. Yamamoto, J. C. Chan, K. R. Mani, L. F. Been, M. Imamura, E. Nakashima, N. Lee, T. Fujisawa, S. Karasawa, W. Wen, C. V. Joglekar, W. Lu, Y. Chang, Y. Xiang, Y. Gao, S. Liu, Y. Song, S. H. Kwak, H. D. Shin, K. S. Park, C. H. D. Fall, J. Y. Kim, P. C. Sham, K. S. L. Lam, W. Zheng, X. Shu, H. Deng, H. Ikegami, G. V. Krishnaveni, D. K. Sanghera, L. Chuang, L. Liu, R. Hu, Y. Kim, M. Daimon, K. Hotta, W. Jia, J. S. Kooner, J. C. Chambers, G. R. Chandak, R. C. Ma, S. Maeda, R. Dorajoo, M. Yokota, R. Takayanagi, N. Kato, X. Lin, R. J. F. Loos

Published in: Diabetologia | Issue 4/2012

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Abstract

Aims/hypothesis

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.

Methods

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.

Results

The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 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.

Conclusions/interpretation

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.
Appendix
Available only for authorised users
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Metadata
Title
Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
Authors
H. Li
T. O. Kilpeläinen
C. Liu
J. Zhu
Y. Liu
C. Hu
Z. Yang
W. Zhang
W. Bao
S. Cha
Y. Wu
T. Yang
A. Sekine
B. Y. Choi
C. S. Yajnik
D. Zhou
F. Takeuchi
K. Yamamoto
J. C. Chan
K. R. Mani
L. F. Been
M. Imamura
E. Nakashima
N. Lee
T. Fujisawa
S. Karasawa
W. Wen
C. V. Joglekar
W. Lu
Y. Chang
Y. Xiang
Y. Gao
S. Liu
Y. Song
S. H. Kwak
H. D. Shin
K. S. Park
C. H. D. Fall
J. Y. Kim
P. C. Sham
K. S. L. Lam
W. Zheng
X. Shu
H. Deng
H. Ikegami
G. V. Krishnaveni
D. K. Sanghera
L. Chuang
L. Liu
R. Hu
Y. Kim
M. Daimon
K. Hotta
W. Jia
J. S. Kooner
J. C. Chambers
G. R. Chandak
R. C. Ma
S. Maeda
R. Dorajoo
M. Yokota
R. Takayanagi
N. Kato
X. Lin
R. J. F. Loos
Publication date
01-04-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 4/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2370-7

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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