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

TitleAssociation of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
Authors
KeywordsAsians
FTO
Meta-analysis
Obesity. Type 2 diabetes
Issue Date2012
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00125/index.htm
Citation
Diabetologia, 2012, v. 55 n. 4, p. 981-995 How to Cite?
AbstractAims/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. © 2012 Springer-Verlag.
Persistent Identifierhttp://hdl.handle.net/10722/147101
ISSN
2014 Impact Factor: 6.671
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Government Research Grants CouncilCUHK 1/04C
Research Grants CouncilCUHK4724/07M
Government of the Hong Kong SARITS/487/09FP
National Institutes of HealthDK078150
TW05596
HL085144
TW008288
R01 AR050496
R21 AG027110
R01 AG026564
R01 AR057049-01A1
R21 AA015973
NIH/FIC KO1 TW006087
NIH/NIDDK R01 DK082766
Specialized Center of ResearchP50 AR055081
National Science Foundation of China81000363
31000554
PhD Programs Foundation of Ministry of Education of China20100201120058
Fundamental Research Funds for the Central Universities
Shanghai Leading Academic Discipline ProjectS30501
National Research Foundation of Korea (NRF)20100020617
Japanese Society for the Promotion of Science17209021
Priority Area 'Applied Genomics'1601223
17019028
18018020
20018026
Korean Ministry of Health Welfare00-PJ3-PG6-GN07-001
National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust
British Heart FoundationSP/04/002
Medical Research CouncilG0700931
Wellcome Trust084723/Z/08/Z
National Institute for Health ResearchRP-PG-040710371
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences2009KIP401
SIBS2008006
Chinese Academy of SciencesKSCX1-YW-02
National Natural Science Foundation of China30930081
National High Technology Research and Development Program (863 Program)2009AA022704
National 973 Program2011CB504002
National Science Council (NSC) of Taiwan95-3112-B002-002
NSC 96-2752-B002-008-PAE
Shanghai Municipality for Basic Research08dj1400601
Program for the National Natural Science Foundation of ChinaNSFC-30872116
New Century Excellent Talents in the University of ChinaNCET-04-0707
Council of Scientific and Industrial Research, Government of IndiaNWP0032
National Heart, Lung, and Blood Institute, National Institutes of Health
US Department of Health and Human ServicesN01WH22110
24152
321002
32105-6
32108-9
32111-13
32115
32118-32119
32122
42107-26
42129-32
44221
National Institute of Diabetes and Digestive and Kidney Diseases from National Institutes of HealthDK062290
RR20649
ES10126
DK56350
Funding Information:

A full list of acknowledgements can be found in the ESM. This work was supported by the following: Hong Kong Government Research Grants Council Central Allocation Scheme (CUHK 1/04C), Research Grants Council Earmarked Research Grant (CUHK4724/07M) and the Innovation and Technology Fund of the Government of the Hong Kong SAR (ITS/487/09FP); National Institutes of Health (DK078150, TW05596, HL085144, TW008288) and pilot funds (RR20649, ES10126, and DK56350); National Institutes of Health (R01 AR050496, R21 AG027110, R01 AG026564, R01 AR057049-01A1, R21 AA015973) and Specialized Center of Research (P50 AR055081) and National Science Foundation of China (81000363, 31000554) and the PhD Programs Foundation of Ministry of Education of China (20100201120058) and the Fundamental Research Funds for the Central Universities, Shanghai Leading Academic Discipline Project (S30501); National Research Foundation of Korea (NRF, no. 20100020617); the Japanese Society for the Promotion of Science (17209021) and of Priority Area 'Applied Genomics' (1601223, 17019028, 18018020, 20018026); the Korea Health 21 R&D Project, Korean Ministry of Health & Welfare (00-PJ3-PG6-GN07-001); the National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0700931), the Wellcome Trust (084723/Z/08/Z) and the National Institute for Health Research (RP-PG-040710371); the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (2009KIP401), the Chief Scientist Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (SIBS2008006), the Knowledge Innovation Program Project of the Chinese Academy of Sciences (KSCX1-YW-02), the National Natural Science Foundation of China (30930081), and National High Technology Research and Development Program (863 Program) (2009AA022704), National 973 Program (2011CB504002); the National Science Council (NSC 95-3112-B002-002, NSC 96-2752-B002-008-PAE) of Taiwan; major program of Shanghai Municipality for Basic Research (08dj1400601), National Natural Science Foundation of China (30800617); National Institute of Health (NIH/FIC KO1 TW006087, NIH/NIDDK R01 DK082766); the Program for the National Natural Science Foundation of China (NSFC-30872116) and New Century Excellent Talents in the University of China (NCET-04-0707); Council of Scientific and Industrial Research, Government of India (NWP0032); the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services (N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221) and the National Institute of Diabetes and Digestive and Kidney Diseases R01 (DK062290) from the National Institutes of Health.

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Hen_HK
dc.contributor.authorKilpeläinen, TOen_HK
dc.contributor.authorLiu, Cen_HK
dc.contributor.authorZhu, Jen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorHu, Cen_HK
dc.contributor.authorYang, Zen_HK
dc.contributor.authorZhang, Wen_HK
dc.contributor.authorBao, Wen_HK
dc.contributor.authorCha, Sen_HK
dc.contributor.authorWu, Yen_HK
dc.contributor.authorYang, Ten_HK
dc.contributor.authorSekine, Aen_HK
dc.contributor.authorChoi, BYen_HK
dc.contributor.authorYajnik, CSen_HK
dc.contributor.authorZhou, Den_HK
dc.contributor.authorTakeuchi, Fen_HK
dc.contributor.authorYamamoto, Ken_HK
dc.contributor.authorChan, JCen_HK
dc.contributor.authorMani, KRen_HK
dc.contributor.authorBeen, LFen_HK
dc.contributor.authorImamura, Men_HK
dc.contributor.authorNakashima, Een_HK
dc.contributor.authorLee, Nen_HK
dc.contributor.authorFujisawa, Ten_HK
dc.contributor.authorKarasawa, Sen_HK
dc.contributor.authorWen, Wen_HK
dc.contributor.authorJoglekar, CVen_HK
dc.contributor.authorLu, Wen_HK
dc.contributor.authorChang, Yen_HK
dc.contributor.authorXiang, Yen_HK
dc.contributor.authorGao, Yen_HK
dc.contributor.authorLiu, Sen_HK
dc.contributor.authorSong, Yen_HK
dc.contributor.authorKwak, SHen_HK
dc.contributor.authorShin, HDen_HK
dc.contributor.authorPark, KSen_HK
dc.contributor.authorFall, CHDen_HK
dc.contributor.authorKim, JYen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorZheng, Wen_HK
dc.contributor.authorShu, Xen_HK
dc.contributor.authorDeng, Hen_HK
dc.contributor.authorIkegami, Hen_HK
dc.contributor.authorKrishnaveni, GVen_HK
dc.contributor.authorSanghera, DKen_HK
dc.contributor.authorChuang, Len_HK
dc.contributor.authorLiu, Len_HK
dc.contributor.authorHu, Ren_HK
dc.contributor.authorKim, Yen_HK
dc.contributor.authorDaimon, Men_HK
dc.contributor.authorHotta, Ken_HK
dc.contributor.authorJia, Wen_HK
dc.contributor.authorKooner, JSen_HK
dc.contributor.authorChambers, JCen_HK
dc.contributor.authorChandak, GRen_HK
dc.contributor.authorMa, RCen_HK
dc.contributor.authorMaeda, Sen_HK
dc.contributor.authorDorajoo, Ren_HK
dc.contributor.authorYokota, Men_HK
dc.contributor.authorTakayanagi, Ren_HK
dc.contributor.authorKato, Nen_HK
dc.contributor.authorLin, Xen_HK
dc.contributor.authorLoos, RJFen_HK
dc.date.accessioned2012-05-25T07:50:47Z-
dc.date.available2012-05-25T07:50:47Z-
dc.date.issued2012en_HK
dc.identifier.citationDiabetologia, 2012, v. 55 n. 4, p. 981-995en_HK
dc.identifier.issn0012-186Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/147101-
dc.description.abstractAims/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. © 2012 Springer-Verlag.en_HK
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00125/index.htmen_HK
dc.relation.ispartofDiabetologiaen_HK
dc.rightsThe Author(s)en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong Licenseen_US
dc.subjectAsiansen_HK
dc.subjectFTOen_HK
dc.subjectMeta-analysisen_HK
dc.subjectObesity. Type 2 diabetesen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAsian Continental Ancestry Group - geneticsen_HK
dc.subject.meshDiabetes Mellitus, Type 2 - geneticsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenetic Association Studiesen_HK
dc.subject.meshGenetic Predisposition to Diseaseen_HK
dc.subject.meshGenotypeen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshObesity - geneticsen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshProteins - geneticsen_HK
dc.titleAssociation of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asiansen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://www.springerlink.com/link-out/?id=2104&code=W2364W4664351657&MUD=MPen_US
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1007/s00125-011-2370-7en_HK
dc.identifier.pmid22109280en_HK
dc.identifier.pmcidPMC3296006-
dc.identifier.scopuseid_2-s2.0-84862564504en_HK
dc.identifier.hkuros213325-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84862564504&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume55en_HK
dc.identifier.issue4en_HK
dc.identifier.spage981en_HK
dc.identifier.epage995en_HK
dc.identifier.eissn1432-0428en_US
dc.identifier.isiWOS:000301182000015-
dc.publisher.placeGermanyen_HK
dc.description.otherSpringer Open Choice, 25 May 2012en_US
dc.identifier.scopusauthoridLi, H=54400364900en_HK
dc.identifier.scopusauthoridKilpeläinen, TO=34067667400en_HK
dc.identifier.scopusauthoridLiu, C=54400181100en_HK
dc.identifier.scopusauthoridZhu, J=54400617000en_HK
dc.identifier.scopusauthoridLiu, Y=54400165100en_HK
dc.identifier.scopusauthoridHu, C=14121598300en_HK
dc.identifier.scopusauthoridYang, Z=25652386800en_HK
dc.identifier.scopusauthoridZhang, W=54400657800en_HK
dc.identifier.scopusauthoridBao, W=35387368700en_HK
dc.identifier.scopusauthoridCha, S=35108847200en_HK
dc.identifier.scopusauthoridWu, Y=54400593600en_HK
dc.identifier.scopusauthoridYang, T=35294141300en_HK
dc.identifier.scopusauthoridSekine, A=7006531399en_HK
dc.identifier.scopusauthoridChoi, BY=41761378100en_HK
dc.identifier.scopusauthoridYajnik, CS=7003959905en_HK
dc.identifier.scopusauthoridZhou, D=25643719100en_HK
dc.identifier.scopusauthoridTakeuchi, F=7103237031en_HK
dc.identifier.scopusauthoridYamamoto, K=35376242800en_HK
dc.identifier.scopusauthoridChan, JC=7403287000en_HK
dc.identifier.scopusauthoridMani, KR=16039875900en_HK
dc.identifier.scopusauthoridBeen, LF=26423574400en_HK
dc.identifier.scopusauthoridImamura, M=49863580600en_HK
dc.identifier.scopusauthoridNakashima, E=7007038951en_HK
dc.identifier.scopusauthoridLee, N=36193858700en_HK
dc.identifier.scopusauthoridFujisawa, T=7402915286en_HK
dc.identifier.scopusauthoridKarasawa, S=23018403400en_HK
dc.identifier.scopusauthoridWen, W=7102171018en_HK
dc.identifier.scopusauthoridJoglekar, CV=16646245000en_HK
dc.identifier.scopusauthoridLu, W=25652669200en_HK
dc.identifier.scopusauthoridChang, Y=27170634500en_HK
dc.identifier.scopusauthoridXiang, Y=7201979437en_HK
dc.identifier.scopusauthoridGao, Y=34770682500en_HK
dc.identifier.scopusauthoridLiu, S=54400264300en_HK
dc.identifier.scopusauthoridSong, Y=8436554700en_HK
dc.identifier.scopusauthoridKwak, SH=25646358500en_HK
dc.identifier.scopusauthoridShin, HD=25651746900en_HK
dc.identifier.scopusauthoridPark, KS=35243240300en_HK
dc.identifier.scopusauthoridFall, CHD=7006584328en_HK
dc.identifier.scopusauthoridKim, JY=54400044400en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridZheng, W=35381589100en_HK
dc.identifier.scopusauthoridShu, X=7102525083en_HK
dc.identifier.scopusauthoridDeng, H=7401775454en_HK
dc.identifier.scopusauthoridIkegami, H=7101684473en_HK
dc.identifier.scopusauthoridKrishnaveni, GV=12771221000en_HK
dc.identifier.scopusauthoridSanghera, DK=35595048100en_HK
dc.identifier.scopusauthoridChuang, L=34569106600en_HK
dc.identifier.scopusauthoridLiu, L=54400211000en_HK
dc.identifier.scopusauthoridHu, R=7202640826en_HK
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dc.identifier.scopusauthoridJia, W=55058008200en_HK
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dc.identifier.scopusauthoridChambers, JC=7402475686en_HK
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dc.identifier.scopusauthoridMaeda, S=7402105147en_HK
dc.identifier.scopusauthoridDorajoo, R=25947407400en_HK
dc.identifier.scopusauthoridYokota, M=7201924070en_HK
dc.identifier.scopusauthoridTakayanagi, R=7005904930en_HK
dc.identifier.scopusauthoridKato, N=7403474204en_HK
dc.identifier.scopusauthoridLin, X=24385545200en_HK
dc.identifier.scopusauthoridLoos, RJF=7006771047en_HK
dc.identifier.citeulike10079597-

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