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

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. ManiL. 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, Yiqing 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

Research output: Contribution to journalArticle

126 Citations (Scopus)

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 [r2>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.

Original languageEnglish (US)
Pages (from-to)981-995
Number of pages15
JournalDiabetologia
Volume55
Issue number4
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

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Type 2 Diabetes Mellitus
Obesity
Alleles
Meta-Analysis
Proxy
Population
Adipose Tissue

Keywords

  • Asians
  • FTO
  • Meta-analysis
  • Obesity. Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians. / 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, Yiqing; Kwak, S. H.; Shin, H. D.; Park, K. S.; Fall, C. H.D.; 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.; Loos, R. J.F.

In: Diabetologia, Vol. 55, No. 4, 01.04.2012, p. 981-995.

Research output: Contribution to journalArticle

Li, H, Kilpeläinen, TO, Liu, C, Zhu, J, Liu, Y, Hu, C, Yang, Z, Zhang, W, Bao, W, Cha, S, Wu, Y, Yang, T, Sekine, A, Choi, BY, Yajnik, CS, Zhou, D, Takeuchi, F, Yamamoto, K, Chan, JC, Mani, KR, Been, LF, Imamura, M, Nakashima, E, Lee, N, Fujisawa, T, Karasawa, S, Wen, W, Joglekar, CV, Lu, W, Chang, Y, Xiang, Y, Gao, Y, Liu, S, Song, Y, Kwak, SH, Shin, HD, Park, KS, Fall, CHD, Kim, JY, Sham, PC, Lam, KSL, Zheng, W, Shu, X, Deng, H, Ikegami, H, Krishnaveni, GV, Sanghera, DK, Chuang, L, Liu, L, Hu, R, Kim, Y, Daimon, M, Hotta, K, Jia, W, Kooner, JS, Chambers, JC, Chandak, GR, Ma, RC, Maeda, S, Dorajoo, R, Yokota, M, Takayanagi, R, Kato, N, Lin, X & Loos, RJF 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, vol. 55, no. 4, pp. 981-995. https://doi.org/10.1007/s00125-011-2370-7
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, Yiqing ; Kwak, S. H. ; Shin, H. D. ; Park, K. S. ; Fall, C. H.D. ; 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. ; Loos, R. J.F. / Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians. In: Diabetologia. 2012 ; Vol. 55, No. 4. pp. 981-995.
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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 [r2>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.",
keywords = "Asians, FTO, Meta-analysis, Obesity. Type 2 diabetes",
author = "H. Li and Kilpel{\"a}inen, {T. O.} and C. Liu and J. Zhu and Y. Liu and C. Hu and Z. Yang and W. Zhang and W. Bao and S. Cha and Y. Wu and T. Yang and A. Sekine and Choi, {B. Y.} and Yajnik, {C. S.} and D. Zhou and F. Takeuchi and K. Yamamoto and Chan, {J. C.} and Mani, {K. R.} and Been, {L. F.} and M. Imamura and E. Nakashima and N. Lee and T. Fujisawa and S. Karasawa and W. Wen and Joglekar, {C. V.} and W. Lu and Y. Chang and Y. Xiang and Y. Gao and S. Liu and Yiqing Song and Kwak, {S. H.} and Shin, {H. D.} and Park, {K. S.} and Fall, {C. H.D.} and Kim, {J. Y.} and Sham, {P. C.} and Lam, {K. S.L.} and W. Zheng and X. Shu and H. Deng and H. Ikegami and Krishnaveni, {G. V.} and Sanghera, {D. K.} and L. Chuang and L. Liu and R. Hu and Y. Kim and M. Daimon and K. Hotta and W. Jia and Kooner, {J. S.} and Chambers, {J. C.} and Chandak, {G. R.} and Ma, {R. C.} and S. Maeda and R. Dorajoo and M. Yokota and R. Takayanagi and N. Kato and X. Lin and Loos, {R. J.F.}",
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volume = "55",
pages = "981--995",
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TY - JOUR

T1 - Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians

AU - Li, H.

AU - Kilpeläinen, T. O.

AU - Liu, C.

AU - Zhu, J.

AU - Liu, Y.

AU - Hu, C.

AU - Yang, Z.

AU - Zhang, W.

AU - Bao, W.

AU - Cha, S.

AU - Wu, Y.

AU - Yang, T.

AU - Sekine, A.

AU - Choi, B. Y.

AU - Yajnik, C. S.

AU - Zhou, D.

AU - Takeuchi, F.

AU - Yamamoto, K.

AU - Chan, J. C.

AU - Mani, K. R.

AU - Been, L. F.

AU - Imamura, M.

AU - Nakashima, E.

AU - Lee, N.

AU - Fujisawa, T.

AU - Karasawa, S.

AU - Wen, W.

AU - Joglekar, C. V.

AU - Lu, W.

AU - Chang, Y.

AU - Xiang, Y.

AU - Gao, Y.

AU - Liu, S.

AU - Song, Yiqing

AU - Kwak, S. H.

AU - Shin, H. D.

AU - Park, K. S.

AU - Fall, C. H.D.

AU - Kim, J. Y.

AU - Sham, P. C.

AU - Lam, K. S.L.

AU - Zheng, W.

AU - Shu, X.

AU - Deng, H.

AU - Ikegami, H.

AU - Krishnaveni, G. V.

AU - Sanghera, D. K.

AU - Chuang, L.

AU - Liu, L.

AU - Hu, R.

AU - Kim, Y.

AU - Daimon, M.

AU - Hotta, K.

AU - Jia, W.

AU - Kooner, J. S.

AU - Chambers, J. C.

AU - Chandak, G. R.

AU - Ma, R. C.

AU - Maeda, S.

AU - Dorajoo, R.

AU - Yokota, M.

AU - Takayanagi, R.

AU - Kato, N.

AU - Lin, X.

AU - Loos, R. J.F.

PY - 2012/4/1

Y1 - 2012/4/1

N2 - 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 [r2>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.

AB - 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 [r2>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.

KW - Asians

KW - FTO

KW - Meta-analysis

KW - Obesity. Type 2 diabetes

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