Article: 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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TitleAssociation of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
AuthorsLi, H32
Kilpeläinen, TO2
Liu, C32
Zhu, J32
Liu, Y22
Hu, C7
Yang, Z31
Zhang, W20
Bao, W21
Cha, S16
Wu, Y40
Yang, T41
Sekine, A26
Choi, BY34
Yajnik, CS39
Zhou, D32
Takeuchi, F29
Yamamoto, K6
Chan, JC15
Mani, KR28
Been, LF42
Imamura, M13
Nakashima, E10
Lee, N11
Fujisawa, T30
Karasawa, S25
Wen, W27
Joglekar, CV39
Lu, W19
Chang, Y23
Xiang, Y33
Gao, Y33
Liu, S9
Song, Y35
Kwak, SH24
Shin, HD17
Park, KS24
Fall, CHD5
Kim, JY16
Sham, PC1
Lam, KSL1
Zheng, W27
Shu, X27
Deng, H12 36 38
Ikegami, H3
Krishnaveni, GV37
Sanghera, DK42
Chuang, L23
Liu, L21
Hu, R31
Kim, Y8
Daimon, M25
Hotta, K26
Jia, W7
Kooner, JS4
Chambers, JC20
Chandak, GR28
Ma, RC15
Maeda, S13
Dorajoo, R4 14
Yokota, M18
Takayanagi, R6
Kato, N29
Lin, X32
Loos, RJF2
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
CitationDiabetologia, 2012, v. 55 n. 4, p. 981-995 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00125-011-2370-7
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.
ISSN0012-186X
2011 Impact Factor: 6.814
2011 SCImago Journal Rankings: 0.651
DOIhttp://dx.doi.org/10.1007/s00125-011-2370-7
ISI Accession Number IDWOS:000301182000015
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.

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLi, H
dc.contributor.authorKilpeläinen, TO
dc.contributor.authorLiu, C
dc.contributor.authorZhu, J
dc.contributor.authorLiu, Y
dc.contributor.authorHu, C
dc.contributor.authorYang, Z
dc.contributor.authorZhang, W
dc.contributor.authorBao, W
dc.contributor.authorCha, S
dc.contributor.authorWu, Y
dc.contributor.authorYang, T
dc.contributor.authorSekine, A
dc.contributor.authorChoi, BY
dc.contributor.authorYajnik, CS
dc.contributor.authorZhou, D
dc.contributor.authorTakeuchi, F
dc.contributor.authorYamamoto, K
dc.contributor.authorChan, JC
dc.contributor.authorMani, KR
dc.contributor.authorBeen, LF
dc.contributor.authorImamura, M
dc.contributor.authorNakashima, E
dc.contributor.authorLee, N
dc.contributor.authorFujisawa, T
dc.contributor.authorKarasawa, S
dc.contributor.authorWen, W
dc.contributor.authorJoglekar, CV
dc.contributor.authorLu, W
dc.contributor.authorChang, Y
dc.contributor.authorXiang, Y
dc.contributor.authorGao, Y
dc.contributor.authorLiu, S
dc.contributor.authorSong, Y
dc.contributor.authorKwak, SH
dc.contributor.authorShin, HD
dc.contributor.authorPark, KS
dc.contributor.authorFall, CHD
dc.contributor.authorKim, JY
dc.contributor.authorSham, PC
dc.contributor.authorLam, KSL
dc.contributor.authorZheng, W
dc.contributor.authorShu, X
dc.contributor.authorDeng, H
dc.contributor.authorIkegami, H
dc.contributor.authorKrishnaveni, GV
dc.contributor.authorSanghera, DK
dc.contributor.authorChuang, L
dc.contributor.authorLiu, L
dc.contributor.authorHu, R
dc.contributor.authorKim, Y
dc.contributor.authorDaimon, M
dc.contributor.authorHotta, K
dc.contributor.authorJia, W
dc.contributor.authorKooner, JS
dc.contributor.authorChambers, JC
dc.contributor.authorChandak, GR
dc.contributor.authorMa, RC
dc.contributor.authorMaeda, S
dc.contributor.authorDorajoo, R
dc.contributor.authorYokota, M
dc.contributor.authorTakayanagi, R
dc.contributor.authorKato, N
dc.contributor.authorLin, X
dc.contributor.authorLoos, RJF
dc.date.accessioned2012-05-25T07:50:47Z
dc.date.available2012-05-25T07:50:47Z
dc.date.issued2012
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.
dc.description.naturepublished_or_final_version
dc.description.otherSpringer Open Choice, 25 May 2012
dc.identifier.citationDiabetologia, 2012, v. 55 n. 4, p. 981-995 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00125-011-2370-7
dc.identifier.citeulike10079597
dc.identifier.doihttp://dx.doi.org/10.1007/s00125-011-2370-7
dc.identifier.eissn1432-0428
dc.identifier.epage995
dc.identifier.isiWOS:000301182000015
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.

dc.identifier.issn0012-186X
2011 Impact Factor: 6.814
2011 SCImago Journal Rankings: 0.651
dc.identifier.issue4
dc.identifier.openurl
dc.identifier.pmid22109280
dc.identifier.scopuseid_2-s2.0-84862564504
dc.identifier.spage981
dc.identifier.urihttp://hdl.handle.net/10722/147101
dc.identifier.volume55
dc.languageEng
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00125/index.htm
dc.publisher.placeGermany
dc.relation.ispartofDiabetologia
dc.relation.referencesReferences in Scopus
dc.rightsThe Author(s)
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.subject.meshAdult
dc.subject.meshAsian Continental Ancestry Group - genetics
dc.subject.meshDiabetes Mellitus, Type 2 - genetics
dc.subject.meshFemale
dc.subject.meshGenetic Association Studies
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshGenotype
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshObesity - genetics
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshProteins - genetics
dc.subjectAsians
dc.subjectFTO
dc.subjectMeta-analysis
dc.subjectObesity. Type 2 diabetes
dc.titleAssociation of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Addenbrooke's Hospital
  3. Kinki University School of Medicine
  4. Hammersmith Hospital
  5. University of Southampton
  6. Kyushu University
  7. Shanghai Jiaotong University
  8. Dong-A University, College of Medicine
  9. David Geffen School of Medicine at UCLA
  10. Chubu Rosai Hospital
  11. University of San Carlos
  12. Beijing Jiaotong Daxue
  13. Riken
  14. Genome Institute of Singapore
  15. Prince of Wales Hospital Hong Kong
  16. Korea Institute of Oriental Medicine
  17. Sogang University
  18. Aichi Gakuin University
  19. Shanghai Institute of Preventive Medicine
  20. Imperial College London
  21. Huazhong University of Science and Technology
  22. Fudan University Shanghai Medical College
  23. National Taiwan University Hospital
  24. Seoul National University
  25. Yamagata University Faculty of Medicine
  26. Kyoto University Faculty of Medicine
  27. Vanderbilt University School of Medicine
  28. Centre for Cellular and Molecular Biology india
  29. National Center for Global Health and Medicine
  30. Osaka University Faculty of Medicine
  31. Huashan Hospital
  32. Shanghai Institute for Biological Sciences Chinese Academy of Sciences
  33. null
  34. HanYang University, College of Medicine
  35. Brigham and Women's Hospital
  36. University of Missouri-Kansas City
  37. Holdsworth Memorial Hospital
  38. University of Shanghai for Science and Technology
  39. King Edward Memorial Hospital India
  40. The University of North Carolina at Chapel Hill
  41. Xi'an Jiaotong University
  42. University of Oklahoma Health Sciences Center