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PMID: 24861553 Published · ppublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

Human molecular genetics ·Vol. 23 ·No. 20 ·2014-10-15 ·Pages 5492-504

Wen W, Zheng W, Okada Y, Takeuchi F, Tabara Y, Hwang JY, Dorajoo R, Li H, Tsai FJ, Yang X, He J, Wu Y, He M, Zhang Y, Liang J, Guo X, Sheu WH, Delahanty R, Guo X, Kubo M, Yamamoto K, Ohkubo T, Go MJ, Liu JJ, Gan W, Chen CC, Gao Y, Li S, Lee NR, Wu C, Zhou X, Song H, Yao J, Lee IT, Long J, Tsunoda T, Akiyama K, Takashima N, Cho YS, Ong RT, Lu L, Chen CH, Tan A, Rice TK, Adair LS, Gui L, Allison M, Lee WJ, Cai Q, Isomura M, Umemura S, Kim YJ, Seielstad M, Hixson J, Xiang YB, Isono M, Kim BJ, Sim X, Lu W, Nabika T, Lee J, Lim WY, Gao YT, Takayanagi R, Kang DH, Wong TY, Hsiung CA, Wu IC, Juang JM, Shi J, Choi BY, Aung T, Hu F, Kim MK, Lim WY, Wang TD, Shin MH, Lee J, Ji BT, Lee YH, Young TL, Shin DH, Chun BY, Cho MC, Han BG, Hwu CM, Assimes TL, Absher D, Yan X, Kim E, Kuo JZ, Kwon S, Taylor KD, Chen YD, Rotter JI, Qi L, Zhu D, Wu T, Mohlke KL, Gu D, Mo Z, Wu JY, Lin X, Miki T, Tai ES, Lee JY, Kato N, Shu XO, Tanaka T

Abstract

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

MeSH Terms
5'-Nucleotidase/genetics Aldehyde Dehydrogenase/genetics Aldehyde Dehydrogenase, Mitochondrial Asians/genetics Blood Proteins/genetics Body Mass Index Cardiac Myosins/genetics Far East Female Genetic Predisposition to Disease Genome-Wide Association Study Glycoproteins/genetics Humans KCNQ1 Potassium Channel/genetics Male Myosin Light Chains/genetics Obesity/genetics Polymorphism, Single Nucleotide Proteinase Inhibitory Proteins, Secretory/genetics
Chemicals
Blood Proteins Glycoproteins ITIH4 protein, human KCNQ1 Potassium Channel KCNQ1 protein, human Myosin Light Chains Proteinase Inhibitory Proteins, Secretory myosin light chain 2 ALDH2 protein, human Aldehyde Dehydrogenase Aldehyde Dehydrogenase, Mitochondrial 5'-Nucleotidase NT5C2 protein, human Cardiac Myosins
Authors & Affiliations
109 authors, click to expand affiliations / ORCID
Wen Wanqing
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Zheng Wei
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Okada Yukinori
Laboratory for Statistical Analysis, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Takeuchi Fumihiko
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Tabara Yasuharu
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hwang Joo-Yeon
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
Dorajoo Rajkumar
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore, Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
Li Huaixing
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Tsai Fuu-Jen
School of Chinese Medicine, Department of Medical Genetics, Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
Yang Xiaobo
Department of Occupational Health and Environmental Health, School of Public Health, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.
He Jiang
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Wu Ying
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
He Meian
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Zhang Yi
State Key Laboratory of Medical Genetics, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai Institute of Hypertension, Shanghai, China.
Liang Jun
Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu 221009, China.
Guo Xiuqing
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
Sheu Wayne Huey-Herng
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, National Defense Medical Center, College of Medicine, Taipei, Taiwan, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Delahanty Ryan
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Guo Xingyi
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Kubo Michiaki
Laboratory for Genotyping Development.
Yamamoto Ken
Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Ohkubo Takayoshi
Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan, Department of Health Science, Shiga University of Medical Science, Otsu, Japan.
Go Min Jin
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
Liu Jian Jun
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Gan Wei
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Chen Ching-Chu
School of Chinese Medicine, Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.
Gao Yong
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China, College of General Practice, Guangxi Medical University, Nanning, Guangxi, China.
Li Shengxu
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Lee Nanette R
USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu, Philippines.
Wu Chen
State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zhou Xueya
Bioinformatics Division, Tsinghua National Laboratory of Information Science and Technology, Beijing, China.
Song Huaidong
State Key Laboratory of Medical Genomics, Ruijin Hospital, Molecular Medical Center, Shanghai Institute of Endocrinology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yao Jie
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
Lee I-Te
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Department of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
Long Jirong
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Tsunoda Tatsuhiko
Laboratory for Medical Science Mathematics.
Akiyama Koichi
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Takashima Naoyuki
Department of Health Science, Shiga University of Medical Science, Otsu, Japan.
Cho Yoon Shin
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea, Department of Biomedical Science, Hallym University, Gangwon-do, Republic of Korea.
Ong Rick Th
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore, NUS Graduate School for Integrative Science and Engineering, Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.
Lu Ling
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Chen Chien-Hsiun
School of Chinese Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Tan Aihua
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.
Rice Treva K
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
Adair Linda S
Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
Gui Lixuan
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Allison Matthew
Department of Family and Preventive Medicine.
Lee Wen-Jane
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Department of Social Work, Tunghai University, Taichung, Taiwan.
Cai Qiuyin
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Isomura Minoru
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Umemura Satoshi
Department of Medical Science and Cardiorenal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
Kim Young Jin
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
Seielstad Mark
Institute of Human Genetics, University of California, San Francisco, USA.
Hixson James
Human Genetics Center, University of Texas School of Public Health, Houston, TX, USA.
Xiang Yong-Bing
Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Isono Masato
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Kim Bong-Jo
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
Sim Xueling
Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.
Lu Wei
Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
Nabika Toru
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Lee Juyoung
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
Lim Wei-Yen
Saw Swee Hock School of Public Health.
Gao Yu-Tang
Department of Epidemiology, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China.
Takayanagi Ryoichi
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kang Dae-Hee
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Wong Tien Yin
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore, Department of Ophthalmology, Yong Loo Lin School of Medicine.
Hsiung Chao Agnes
Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Wu I-Chien
Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Juang Jyh-Ming Jimmy
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Shi Jiajun
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Choi Bo Youl
Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Aung Tin
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore, Department of Ophthalmology, Yong Loo Lin School of Medicine.
Hu Frank
Department of Epidemiology, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA.
Kim Mi Kyung
Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Lim Wei Yen
Saw Swee Hock School of Public Health.
Wang Tzung-Dao
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Shin Min-Ho
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Lee Jeannette
Saw Swee Hock School of Public Health.
Ji Bu-Tian
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Lee Young-Hoon
Department of Preventive Medicine & Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Republic of Korea.
Young Terri L
Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA, Division of Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
Shin Dong Hoon
Department of Preventive Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
Chun Byung-Yeol
Department of Preventive Medicine, School of Medicine, and Health Promotion Research Center, Kyungpook National University, Daegu, Republic of Korea.
Cho Myeong-Chan
National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
Han Bok-Ghee
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
Hwu Chii-Min
School of Medicine, National Yang-Ming University, Taipei, Taiwan, Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Assimes Themistocles L
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Absher Devin
HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
Yan Xiaofei
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
Kim Eric
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
Kuo Jane Z
NShiley Eye Center, Department of Ophthalmology, University of California at San Diego, La Jolla, CA, USA.
Kwon Soonil
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
Taylor Kent D
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
Chen Yii-Der I
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
Rotter Jerome I
Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
Qi Lu
Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
Zhu Dingliang
State Key Laboratory of Medical Genetics, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai Institute of Hypertension, Shanghai, China.
Wu Tangchun
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Mohlke Karen L
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Gu Dongfeng
Department of Evidence Based Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and National Center for Cardiovascular Diseases, Beijing, China.
Mo Zengnan
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China, Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Wu Jer-Yuarn
School of Chinese Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Lin Xu
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Miki Tetsuro
Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Japan.
Tai E Shyong
Saw Swee Hock School of Public Health, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, and National University Health System, Singapore, Singapore Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
Lee Jong-Young
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
Kato Norihiro
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Shu Xiao-Ou
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA, [email protected].
Tanaka Toshihiro
Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan, Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan, Division of Disease Diversity, Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
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Article Info
Journal
Human molecular genetics
Abbr.
Hum Mol Genet
ISSN
1460-2083
DOI
10.1093/hmg/ddu248
Email
[email protected]
Published
2014-10-15
Epub
2014-00-26
Pages
5492-504
Language
English
Region
England
NLM ID
9208958
PMCID
PMC4168820
Subset
IM
Grants
NHLBI NIH HHS · R01HL087263 · United States
NIEHS NIH HHS · P30 ES010126 · United States
FIC NIH HHS · TW008288 · United States
NCI NIH HHS · R01CA092585 · United States
NCRR NIH HHS · RR-024156 · United States
NHLBI NIH HHS · R01HL090682 · United States
NCI NIH HHS · R01CA148667 · United States
FIC NIH HHS · TW05596 · United States
NIDDK NIH HHS · P30 DK063491 · United States
NHLBI NIH HHS · N01-HC-95169 · United States
NIDDK NIH HHS · DK078616 · United States
NCI NIH HHS · R01CA082729 · United States
NIDDK NIH HHS · DK078150 · United States
NHLBI NIH HHS · N02-HL-6-4278 · United States
NHLBI NIH HHS · N01-HC-95159 · United States
NCI NIH HHS · UM1 CA173640 · United States
NICHD NIH HHS · K12 HD043451 · United States
NCATS NIH HHS · UL1 TR000124 · United States
NCI NIH HHS · R01CA064277 · United States
NIEHS NIH HHS · ES10126 · United States
NCI NIH HHS · R01CA122364 · United States
NCRR NIH HHS · RR20649 · United States
NIDDK NIH HHS · P30 DK046200 · United States
NIDDK NIH HHS · DK56350 · United States
NHLBI NIH HHS · HL085144 · United States
NCI NIH HHS · R01 CA148667 · United States
NHLBI NIH HHS · U01HL072507 · United States
NIDDK NIH HHS · DK091718 · United States
NHLBI NIH HHS · R01 HL087263 · United States
NCI NIH HHS · R37CA070867 · United States
NHLBI NIH HHS · HL087647 · United States
NHLBI NIH HHS · HL071981 · United States
NCI NIH HHS · R01CA124558 · United States
NHLBI NIH HHS · R01 HL090682 · United States
NCI NIH HHS · UM1 CA182910 · United States
NIDDK NIH HHS · R01 DK078150 · United States
NIDDK NIH HHS · DK46200 · United States
External Links
PubMed source DOI: 10.1093/hmg/ddu248 PMC Full Text View journal details
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