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

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
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/m(2) 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.
0012-186X
981-995
Li, H.
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Kilpeläinen, T.O.
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Liu, C.
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Kwak, S.H.
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Sham, P.C.
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Ikegami, H
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Yokota, M.
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Takayanagi, R.
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Loos, R.J.F
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Li, H.
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Kilpeläinen, T.O.
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Liu, C.
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Zhu, J.
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Liu, Y.
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Hu, C.
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Yang, Z.
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Zhang, W.
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Bao, W.
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Cha, S.
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Wu, Y.
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Yang, T.
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Sekine, A.
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Choi, B.Y.
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Yajnik, C.S.
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Zhou, D.
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Takeuchi, F.
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Yamamoto, K.
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Chan, J.C.
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Mani, K.R.
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Been, L.F.
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Imamura, M.
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Nakashima, E.
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Lee, N.
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Fujisawa, T
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Karasawa, S.
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Wen, W.
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Joglekar, C.V.
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Chang, Y.
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Xiang, Y.
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Gao, Y.
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Liu, S.
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Song, Y.
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Kwak, S.H.
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Shin, H.D.
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Park, K.S.
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Fall, C.H.
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Sham, P.C.
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Lam, K.S.L.
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Zheng, W.
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Shu, X.
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Deng, H.
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Ikegami, H
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Krishnaveni, G.V.
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Takayanagi, R.
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Kato, N.
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Lin, X.
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Loos, R.J.F
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Li, H., Kilpeläinen, T.O., Liu, C., Zhu, J., Liu, Y., Hu, C., Yang, Z., Zhang, W., Bao, W., Cha, S., Wu, Y., Yang, T., Sekine, A., Choi, B.Y., Yajnik, C.S., Zhou, D., Takeuchi, F., Yamamoto, K., Chan, J.C., Mani, K.R., Been, L.F., Imamura, M., Nakashima, E., Lee, N., Fujisawa, T, Karasawa, S., Wen, W., Joglekar, C.V., Lu, W., Chang, Y., Xiang, Y., Gao, Y., Liu, S., Song, Y., Kwak, S.H., Shin, H.D., Park, K.S., Fall, C.H., Kim, J.Y., Sham, P.C., Lam, K.S.L., Zheng, W., Shu, X., Deng, H., Ikegami, H, Krishnaveni, G.V., Sanghera, D.K., Chuang, L., Liu, L., Hu, R., Kim, Y., Daimon, M., Hotta, K., Jia, W., Kooner, J.S., Chambers, J.C., Chandak, G.R., Ma, R.C., Maeda, S., Dorajoo, R., Yokota, M., Takayanagi, R., Kato, N., Lin, X. and Loos, R.J.F (2012) Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians. Diabetologia, 55 (4), 981-995. (doi:10.1007/s00125-011-2370-7). (PMID:22109280)

Record type: Article

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/m(2) 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.

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Published date: April 2012
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 352574
URI: http://eprints.soton.ac.uk/id/eprint/352574
ISSN: 0012-186X
PURE UUID: 0a967e31-03be-42db-8ea4-4c045e673cd1
ORCID for C.H. Fall: ORCID iD orcid.org/0000-0003-4402-5552

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Date deposited: 16 May 2013 13:21
Last modified: 18 Feb 2021 16:37

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Contributors

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

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