Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

Minako Imamura; Atsushi Takahashi; Toshimasa Yamauchi; Kazuo Hara; Kazuki Yasuda; Niels Grarup; Wei Zhao; Xu Wang; Alicia Huerta-Chagoya; Cheng Hu; Sanghoon Moon; Jirong Long; Soo Heon Kwak; Asif Rasheed; Richa Saxena; Ronald C.W. Ma; Yukinori Okada; Minoru Iwata; Jun Hosoe; Nobuhiro Shojima; Minaka Iwasaki; Hayato Fujita; Ken Suzuki; John Danesh; Torben Jørgensen; Marit E. Jørgensen; Daniel R. Witte; Ivan Brandslund; Cramer Christensen; Torben Hansen; Josep M. Mercader; Jason Flannick; Hortensia Moreno-Macías; Noël P. Burtt; Rong Zhang; Young Jin Kim; Wei Zheng; Jai Rup Singh; Claudia H.T. Tam; Hiroshi Hirose; Hiroshi Maegawa; Chikako Ito; Kohei Kaku; Hirotaka Watada; Yasushi Tanaka; Kazuyuki Tobe; Ryuzo Kawamori; Michiaki Kubo; Yoon Shin Cho; Juliana C.N. Chan; Dharambir Sanghera; Philippe Frossard; Kyong Soo Park; Xiao Ou Shu; Bong Jo Kim; Jose C. Florez; Teresa Tusié-Luna; Weiping Jia; E. Shyong Tai; Oluf Pedersen; Danish Saleheen; Shiro Maeda; Takashi Kadowaki

doi:10.1038/ncomms10531

Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

Minako Imamura, Atsushi Takahashi, Toshimasa Yamauchi, Kazuo Hara, Kazuki Yasuda, Niels Grarup, Wei Zhao, Xu Wang, Alicia Huerta-Chagoya, Cheng Hu, Sanghoon Moon, Jirong Long, Soo Heon Kwak, Asif Rasheed, Richa Saxena, Ronald C.W. Ma, Yukinori Okada, Minoru Iwata, Jun Hosoe, Nobuhiro ShojimaMinaka Iwasaki, Hayato Fujita, Ken Suzuki, John Danesh, Torben Jørgensen, Marit E. Jørgensen, Daniel R. Witte, Ivan Brandslund, Cramer Christensen, Torben Hansen, Josep M. Mercader, Jason Flannick, Hortensia Moreno-Macías, Noël P. Burtt, Rong Zhang, Young Jin Kim, Wei Zheng, Jai Rup Singh, Claudia H.T. Tam, Hiroshi Hirose, Hiroshi Maegawa, Chikako Ito, Kohei Kaku, Hirotaka Watada, Yasushi Tanaka, Kazuyuki Tobe, Ryuzo Kawamori, Michiaki Kubo, Yoon Shin Cho, Juliana C.N. Chan, Dharambir Sanghera, Philippe Frossard, Kyong Soo Park, Xiao Ou Shu, Bong Jo Kim, Jose C. Florez, Teresa Tusié-Luna, Weiping Jia, E. Shyong Tai, Oluf Pedersen, Danish Saleheen, Shiro Maeda, Takashi Kadowaki

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Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10^-8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.

本文言語	English
論文番号	10531
ジャーナル	Nature communications
巻	7
DOI	https://doi.org/10.1038/ncomms10531
出版ステータス	Published - 2016 1月 28

ASJC Scopus subject areas

化学 (全般)
生化学、遺伝学、分子生物学（全般）
一般
物理学および天文学（全般）

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10.1038/ncomms10531

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Imamura, M., Takahashi, A., Yamauchi, T., Hara, K., Yasuda, K., Grarup, N., Zhao, W., Wang, X., Huerta-Chagoya, A., Hu, C., Moon, S., Long, J., Kwak, S. H., Rasheed, A., Saxena, R., Ma, R. C. W., Okada, Y., Iwata, M., Hosoe, J., ... Kadowaki, T. (2016). Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes. Nature communications, 7, [10531]. https://doi.org/10.1038/ncomms10531

Imamura, M, Takahashi, A, Yamauchi, T, Hara, K, Yasuda, K, Grarup, N, Zhao, W, Wang, X, Huerta-Chagoya, A, Hu, C, Moon, S, Long, J, Kwak, SH, Rasheed, A, Saxena, R, Ma, RCW, Okada, Y, Iwata, M, Hosoe, J, Shojima, N, Iwasaki, M, Fujita, H, Suzuki, K, Danesh, J, Jørgensen, T, Jørgensen, ME, Witte, DR, Brandslund, I, Christensen, C, Hansen, T, Mercader, JM, Flannick, J, Moreno-Macías, H, Burtt, NP, Zhang, R, Kim, YJ, Zheng, W, Singh, JR, Tam, CHT, Hirose, H, Maegawa, H, Ito, C, Kaku, K, Watada, H, Tanaka, Y, Tobe, K, Kawamori, R, Kubo, M, Cho, YS, Chan, JCN, Sanghera, D, Frossard, P, Park, KS, Shu, XO, Kim, BJ, Florez, JC, Tusié-Luna, T, Jia, W, Tai, ES, Pedersen, O, Saleheen, D, Maeda, S & Kadowaki, T 2016, 'Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes', Nature communications, vol. 7, 10531. https://doi.org/10.1038/ncomms10531

@article{1aaf8daa142c41589a2b242028420368,

title = "Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes",

abstract = "Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10-8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.",

author = "Minako Imamura and Atsushi Takahashi and Toshimasa Yamauchi and Kazuo Hara and Kazuki Yasuda and Niels Grarup and Wei Zhao and Xu Wang and Alicia Huerta-Chagoya and Cheng Hu and Sanghoon Moon and Jirong Long and Kwak, {Soo Heon} and Asif Rasheed and Richa Saxena and Ma, {Ronald C.W.} and Yukinori Okada and Minoru Iwata and Jun Hosoe and Nobuhiro Shojima and Minaka Iwasaki and Hayato Fujita and Ken Suzuki and John Danesh and Torben J{\o}rgensen and J{\o}rgensen, {Marit E.} and Witte, {Daniel R.} and Ivan Brandslund and Cramer Christensen and Torben Hansen and Mercader, {Josep M.} and Jason Flannick and Hortensia Moreno-Mac{\'i}as and Burtt, {No{\"e}l P.} and Rong Zhang and Kim, {Young Jin} and Wei Zheng and Singh, {Jai Rup} and Tam, {Claudia H.T.} and Hiroshi Hirose and Hiroshi Maegawa and Chikako Ito and Kohei Kaku and Hirotaka Watada and Yasushi Tanaka and Kazuyuki Tobe and Ryuzo Kawamori and Michiaki Kubo and Cho, {Yoon Shin} and Chan, {Juliana C.N.} and Dharambir Sanghera and Philippe Frossard and Park, {Kyong Soo} and Shu, {Xiao Ou} and Kim, {Bong Jo} and Florez, {Jose C.} and Teresa Tusi{\'e}-Luna and Weiping Jia and Tai, {E. Shyong} and Oluf Pedersen and Danish Saleheen and Shiro Maeda and Takashi Kadowaki",

note = "Funding Information: The Mexican/Latino association data were provided by SIGMA T2D Consortium (see Supplementary Note for the contributors list). Data on glycaemic traits in European populations have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org/. Data on GWAS meta-analysis for T2D in European populations have been contributed by DIAGRAM consortium and have been downloaded from http://diagram-consortium.org/. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology-Japan. The work of the Shanghai Jiao Tong University was supported from grants from the National 973 Program (2011CB504001), 863 Program (2012AA02A509) and National Science Foundation of China (81322010). R.C.W.M. and J.C.N.C. acknowledge support from the Hong Kong Foundation for Research and Development in Diabetes, established under the auspices of the Chinese University of Hong Kong, the Innovation and Technology Fund (ITS/088/08 and ITS/487/09FP)), and the Research Grants Council Theme-based Research Scheme (T12–402/13-N). The work by the Shanghai Diabetes Genetic Study (SDGS) was supported in part by the US National Institutes of Health grants R37CA070867, R01CA124558, R01CA64277 and UL1 RR024975, the Department of Defense Idea Award BC050791, Vanderbilt Ingram professorship funds and the Allen Foundation Fund. We thank the dedicated investigators and staff members from research teams at Vanderbilt University, Shanghai Cancer Institute and the Shanghai Institute of Preventive Medicine, and especially the study participants for their contributions in the studies. This study was provided with data from the Korean Genome Analysis Project (4845-301), the Korean Genome and Epidemiology Study (4851-302) and Korea Biobank Project (4851-307, KBP-2013-11 and KBP-2014-68) that were supported by the Korea Center for Disease Control and Prevention, Republic of Korea. This research was supported by an intramural grant from the Korea National Institute of Health (2014-NI73001-00), Republic of Korea. This study was supported by a grant of the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C0060). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). The Danish studies, Inter99 and Health2006, were partly funded by the Lundbeck Foundation and produced by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp, www.lucamp.org). The Asian Indian Diabetic Heart Study/Sikh Diabetes Study (AIDHS/SDS) was supported by the National Institute of Health grants KO1TW006087 funded by the Fogarty International Center, R01DK082766 funded by National Institute of Diabetes and Digestive and Kidney Diseases, and a seed grant from University of Oklahoma Health Sciences Center, Oklahoma City, USA. We thank the research participants for their contribution and support for making this study possible. A.H.C. was supported by a fellowship from CONACyT-Mexico. J.M.M. was supported by Sara Borrell Fellowship from the Instituto Carlos III, grant SEV-2011-00067 of Severo Ochoa Program and EMBO short-term fellowship, EFSD/Lilly research fellowship and Beatriu de Pin{\'o}s fellowship from the Agency for Management of University and Research Grants (AGAUR). SIGMA study was supported by the Slim Foundation. Y.S.C. acknowledges support from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2012R1A2A1A03006155). Field-work, genotyping and standard clinical chemistry assays in PROMIS were principally supported by grants awarded to the University of Cambridge from the British Heart Foundation, UK Medical Research Council, Wellcome Trust, EU Framework 6-funded Bloodomics Integrated Project, Pfizer, Novartis and Merck. J.D. acknowledges that this work was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834) and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). Publisher Copyright: {\textcopyright} 2016, Nature Publishing Group. All rights reserved.",

year = "2016",

month = jan,

day = "28",

doi = "10.1038/ncomms10531",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

AU - Imamura, Minako

AU - Takahashi, Atsushi

AU - Yamauchi, Toshimasa

AU - Hara, Kazuo

AU - Yasuda, Kazuki

AU - Grarup, Niels

AU - Zhao, Wei

AU - Wang, Xu

AU - Huerta-Chagoya, Alicia

AU - Hu, Cheng

AU - Moon, Sanghoon

AU - Long, Jirong

AU - Kwak, Soo Heon

AU - Rasheed, Asif

AU - Saxena, Richa

AU - Ma, Ronald C.W.

AU - Okada, Yukinori

AU - Iwata, Minoru

AU - Hosoe, Jun

AU - Shojima, Nobuhiro

AU - Iwasaki, Minaka

AU - Fujita, Hayato

AU - Suzuki, Ken

AU - Danesh, John

AU - Jørgensen, Torben

AU - Jørgensen, Marit E.

AU - Witte, Daniel R.

AU - Brandslund, Ivan

AU - Christensen, Cramer

AU - Hansen, Torben

AU - Mercader, Josep M.

AU - Flannick, Jason

AU - Moreno-Macías, Hortensia

AU - Burtt, Noël P.

AU - Zhang, Rong

AU - Kim, Young Jin

AU - Zheng, Wei

AU - Singh, Jai Rup

AU - Tam, Claudia H.T.

AU - Hirose, Hiroshi

AU - Maegawa, Hiroshi

AU - Ito, Chikako

AU - Kaku, Kohei

AU - Watada, Hirotaka

AU - Tanaka, Yasushi

AU - Tobe, Kazuyuki

AU - Kawamori, Ryuzo

AU - Kubo, Michiaki

AU - Cho, Yoon Shin

AU - Chan, Juliana C.N.

AU - Sanghera, Dharambir

AU - Frossard, Philippe

AU - Park, Kyong Soo

AU - Shu, Xiao Ou

AU - Kim, Bong Jo

AU - Florez, Jose C.

AU - Tusié-Luna, Teresa

AU - Jia, Weiping

AU - Tai, E. Shyong

AU - Pedersen, Oluf

AU - Saleheen, Danish

AU - Maeda, Shiro

AU - Kadowaki, Takashi

N1 - Funding Information: The Mexican/Latino association data were provided by SIGMA T2D Consortium (see Supplementary Note for the contributors list). Data on glycaemic traits in European populations have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org/. Data on GWAS meta-analysis for T2D in European populations have been contributed by DIAGRAM consortium and have been downloaded from http://diagram-consortium.org/. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology-Japan. The work of the Shanghai Jiao Tong University was supported from grants from the National 973 Program (2011CB504001), 863 Program (2012AA02A509) and National Science Foundation of China (81322010). R.C.W.M. and J.C.N.C. acknowledge support from the Hong Kong Foundation for Research and Development in Diabetes, established under the auspices of the Chinese University of Hong Kong, the Innovation and Technology Fund (ITS/088/08 and ITS/487/09FP)), and the Research Grants Council Theme-based Research Scheme (T12–402/13-N). The work by the Shanghai Diabetes Genetic Study (SDGS) was supported in part by the US National Institutes of Health grants R37CA070867, R01CA124558, R01CA64277 and UL1 RR024975, the Department of Defense Idea Award BC050791, Vanderbilt Ingram professorship funds and the Allen Foundation Fund. We thank the dedicated investigators and staff members from research teams at Vanderbilt University, Shanghai Cancer Institute and the Shanghai Institute of Preventive Medicine, and especially the study participants for their contributions in the studies. This study was provided with data from the Korean Genome Analysis Project (4845-301), the Korean Genome and Epidemiology Study (4851-302) and Korea Biobank Project (4851-307, KBP-2013-11 and KBP-2014-68) that were supported by the Korea Center for Disease Control and Prevention, Republic of Korea. This research was supported by an intramural grant from the Korea National Institute of Health (2014-NI73001-00), Republic of Korea. This study was supported by a grant of the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C0060). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). The Danish studies, Inter99 and Health2006, were partly funded by the Lundbeck Foundation and produced by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp, www.lucamp.org). The Asian Indian Diabetic Heart Study/Sikh Diabetes Study (AIDHS/SDS) was supported by the National Institute of Health grants KO1TW006087 funded by the Fogarty International Center, R01DK082766 funded by National Institute of Diabetes and Digestive and Kidney Diseases, and a seed grant from University of Oklahoma Health Sciences Center, Oklahoma City, USA. We thank the research participants for their contribution and support for making this study possible. A.H.C. was supported by a fellowship from CONACyT-Mexico. J.M.M. was supported by Sara Borrell Fellowship from the Instituto Carlos III, grant SEV-2011-00067 of Severo Ochoa Program and EMBO short-term fellowship, EFSD/Lilly research fellowship and Beatriu de Pinós fellowship from the Agency for Management of University and Research Grants (AGAUR). SIGMA study was supported by the Slim Foundation. Y.S.C. acknowledges support from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2012R1A2A1A03006155). Field-work, genotyping and standard clinical chemistry assays in PROMIS were principally supported by grants awarded to the University of Cambridge from the British Heart Foundation, UK Medical Research Council, Wellcome Trust, EU Framework 6-funded Bloodomics Integrated Project, Pfizer, Novartis and Merck. J.D. acknowledges that this work was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834) and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). Publisher Copyright: © 2016, Nature Publishing Group. All rights reserved.

PY - 2016/1/28

Y1 - 2016/1/28

N2 - Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10-8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.

AB - Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10-8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.

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U2 - 10.1038/ncomms10531

DO - 10.1038/ncomms10531

M3 - Article

C2 - 26818947

AN - SCOPUS:84956612031

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 10531

ER -

Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

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