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; L F Been; M Imamura; T O Kilpeläinen; C Liu; E Nakashima; J Zhu; N Lee; Y Liu; T Fujisawa; C Hu; S Karasawa; Z Yang; C V Joglekar; W Zhang; W Lu; Y Chang; W Bao; S Cha; Y Xiang; T Yang; S Liu; Y Wu; A Sekine; S H Kwak; B Y Choi; H D Shin; C S Yajnik; K S Park; D Zhou; C H D Fall; F Takeuchi; P C Sham; K Yamamoto; H Deng; J C Chan; H Ikegami; K R Mani; D K Sanghera; G V Krishnaveni; L Chuang; 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 Shu; Y Gao; W Wen; K S L Lam; J Y Kim; W Zheng; R J F Loos; Y Song; L Liu; X Lin

doi:10.1007/s00125-011-2370-7

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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

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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

H Li, L F Been, M Imamura, T O Kilpeläinen, C Liu, E Nakashima, J Zhu, N Lee, Y Liu, T Fujisawa, …

Diabetologia, Vol.55(4), pp.981-995

04/2012

DOI: 10.1007/s00125-011-2370-7

PMCID: PMC3296006

PMID: 22109280

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Abstract

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 × 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. 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.

Genetic Predisposition to Disease

Genetic Association Studies

Diabetes Mellitus, Type 2 - genetics

Humans

Asian Continental Ancestry Group - genetics

Alpha-Ketoglutarate-Dependent Dioxygenase FTO

Genotype

Male

Obesity - genetics

Proteins - genetics

Adult

Female

Polymorphism, Single Nucleotide

Details

Title: Subtitle: Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
Creators: H Li - Shanghai Institutes for Biological Sciences
L F Been
M Imamura
T O Kilpeläinen
C Liu - Shanghai Institutes for Biological Sciences
E Nakashima
J Zhu - Shanghai Institutes for Biological Sciences
N Lee
Y Liu - Fudan University
T Fujisawa
C Hu
S Karasawa
Z Yang
C V Joglekar
W Zhang - Imperial College London
W Lu
Y Chang
W Bao
S Cha
Y Xiang
T Yang
S Liu - University of California, Los Angeles
Y Wu - University of North Carolina at Chapel Hill
A Sekine
S H Kwak
B Y Choi
H D Shin
C S Yajnik
K S Park - Seoul National University
D Zhou - Chinese Academy of Sciences
C H D Fall
F Takeuchi
P C Sham
K Yamamoto
H Deng
J C Chan
H Ikegami
K R Mani
D K Sanghera
G V Krishnaveni
L Chuang
R Hu
Y Kim - Dong-A University
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 Shu - Vanderbilt University School of Medicine
Y Gao - Shanghai Cancer Institute
W Wen - Vanderbilt University
K S L Lam - University of Hong Kong
J Y Kim - Korea Institute of Oriental Medicine
W Zheng - Vanderbilt University
R J F Loos
Y Song - Brigham and Women's Hospital
L Liu - Huazhong University of Science and Technology
X Lin - Shanghai Institutes for Biological Sciences
Resource Type: Journal article
Publication Details: Diabetologia, Vol.55(4), pp.981-995
DOI: 10.1007/s00125-011-2370-7
PMID: 22109280
PMCID: PMC3296006
NLM abbreviation: Diabetologia
ISSN: 1432-0428
eISSN: 1432-0428
Publisher: Germany
Grant note: SP/04/002 / British Heart Foundation MC_U106188470 / Medical Research Council R37 CA070867 / NCI NIH HHS 079877 / Wellcome Trust RR20649 / NCRR NIH HHS ES10126 / NIEHS NIH HHS 083460 / Wellcome Trust N01WH32100-2 / WHI NIH HHS N01WH32115 / WHI NIH HHS N01WH24152 / WHI NIH HHS MC_UP_A620_1016 / Medical Research Council KO1 TW006087 / FIC NIH HHS N01WH42107-26 / WHI NIH HHS P30 ES010126 / NIEHS NIH HHS HL085144 / NHLBI NIH HHS R01 CA082729 / NCI NIH HHS N01WH44221 / WHI NIH HHS DK078150 / NIDDK NIH HHS 059609 / Wellcome Trust G0601966 / Medical Research Council R01 CA064277 / NCI NIH HHS N01WH32122 / WHI NIH HHS MR/J000094/1 / Medical Research Council N01WH32108-9 / WHI NIH HHS R01 DK078150 / NIDDK NIH HHS N01WH42129-32 / WHI NIH HHS TW05596 / FIC NIH HHS MC_U147574246 / Medical Research Council (084723/Z/08/Z / Wellcome Trust R01 AR057049-01A1 / NIAMS NIH HHS DK56350 / NIDDK NIH HHS N01WH32111-13 / WHI NIH HHS G0700931 / Medical Research Council TW008288 / FIC NIH HHS G0400519 / Medical Research Council N01WH32105-6 / WHI NIH HHS N01WH32118-9 / WHI NIH HHS
Language: English
Date published: 04/2012
Academic Unit: Epidemiology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9983995173702771

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