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; Tuomas Oskari Kilpeläinen; C Liu; Jie Zhu; Y Liu; C Hu; Z Yang; W Zhang; W Bao; Seung-Tae Cha; Y Wu; T Yang; A Sekine; B Y Choi; C S Yajnik; Dao Zhou; F Takeuchi; K Yamamoto; J C Chan; K R Mani; L F Been; M Imamura; E Nakashima; N Lee; T Fujisawa; S Karasawa; Wan Wen; C V Joglekar; W Lu; Y Chang; Y Xiang; Y Gao; S Liu; Y Song; S H Kwak; H D Shin; Kiwoo Park; C H D Fall; J Y Kim; P C Sham; K S L Lam; W Zheng; X Shu; Hong 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; Xue Lin; R J F Loos

doi:10.1007/s00125-011-2370-7

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, Tuomas Oskari Kilpeläinen, C Liu, Jie Zhu, Y Liu, C Hu, Z Yang, W Zhang, W Bao, Seung-Tae Cha, Y Wu, T Yang, A Sekine, B Y Choi, C S Yajnik, Dao Zhou, F Takeuchi, K Yamamoto, J C Chan, K R ManiL F Been, M Imamura, E Nakashima, N Lee, T Fujisawa, S Karasawa, Wan Wen, C V Joglekar, W Lu, Y Chang, Y Xiang, Y Gao, S Liu, Y Song, S H Kwak, H D Shin, Kiwoo Park, C H D Fall, J Y Kim, P C Sham, K S L Lam, W Zheng, X Shu, Hong 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, Xue Lin, R J F Loos

Biomedicinsk Institut

141 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Diabetologia
Vol/bind	55
Udgave nummer	4
Sider (fra-til)	981-95
Antal sider	15
ISSN	0012-186X
DOI	https://doi.org/10.1007/s00125-011-2370-7
Status	Udgivet - apr. 2012

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10.1007/s00125-011-2370-7

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Li, H., Oskari Kilpeläinen, T., Liu, C., Zhu, J., Liu, Y., Hu, C., Yang, Z., Zhang, W., Bao, W., Cha, S-T., Wu, Y., Yang, T., Sekine, A., Choi, B. Y., Yajnik, C. S., Zhou, D., Takeuchi, F., Yamamoto, K., Chan, J. C., ... 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), 981-95. https://doi.org/10.1007/s00125-011-2370-7

Li, H, Oskari Kilpeläinen, T, Liu, C, Zhu, J, Liu, Y, Hu, C, Yang, Z, Zhang, W, Bao, W, Cha, S-T, 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, K, 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, bind 55, nr. 4, s. 981-95. https://doi.org/10.1007/s00125-011-2370-7

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

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 = "Adult, Asian Continental Ancestry Group, Diabetes Mellitus, Type 2, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Male, Obesity, Polymorphism, Single Nucleotide, Proteins",

author = "H Li and {Oskari Kilpel{\"a}inen}, Tuomas and C Liu and Jie Zhu and Y Liu and C Hu and Z Yang and W Zhang and W Bao and Seung-Tae Cha and Y Wu and T Yang and A Sekine and Choi, {B Y} and Yajnik, {C S} and Dao 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 Wan Wen and Joglekar, {C V} and W Lu and Y Chang and Y Xiang and Y Gao and S Liu and Y Song and Kwak, {S H} and Shin, {H D} and Kiwoo Park 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 Hong 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 Xue Lin and Loos, {R J F}",

year = "2012",

month = apr,

doi = "10.1007/s00125-011-2370-7",

language = "English",

volume = "55",

pages = "981--95",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "4",

}

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 - Oskari Kilpeläinen, Tuomas

AU - Liu, C

AU - Zhu, Jie

AU - Liu, Y

AU - Hu, C

AU - Yang, Z

AU - Zhang, W

AU - Bao, W

AU - Cha, Seung-Tae

AU - Wu, Y

AU - Yang, T

AU - Sekine, A

AU - Choi, B Y

AU - Yajnik, C S

AU - Zhou, Dao

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, Wan

AU - Joglekar, C V

AU - Lu, W

AU - Chang, Y

AU - Xiang, Y

AU - Gao, Y

AU - Liu, S

AU - Song, Y

AU - Kwak, S H

AU - Shin, H D

AU - Park, Kiwoo

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, Hong

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, Xue

AU - Loos, R J F

PY - 2012/4

Y1 - 2012/4

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 - Adult

KW - Asian Continental Ancestry Group

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Male

KW - Obesity

KW - Polymorphism, Single Nucleotide

KW - Proteins

U2 - 10.1007/s00125-011-2370-7

DO - 10.1007/s00125-011-2370-7

M3 - Journal article

C2 - 22109280

SN - 0012-186X

VL - 55

SP - 981

EP - 995

JO - Diabetologia

JF - Diabetologia

IS - 4

ER -

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

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