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Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits.
Peng, Qianqian; Liu, Xinxuan; Li, Wenran; Jing, Han; Li, Jiarui; Gao, Xingjian; Luo, Qi; Breeze, Charles E; Pan, Siyu; Zheng, Qiwen; Li, Guochao; Qian, Jiaqiang; Yuan, Liyun; Yuan, Na; You, Chenglong; Du, Siyuan; Zheng, Yuanting; Yuan, Ziyu; Tan, Jingze; Jia, Peilin; Wang, Jiucun; Zhang, Guoqing; Lu, Xianping; Shi, Leming; Guo, Shicheng; Liu, Yun; Ni, Ting; Wen, Bo; Zeng, Changqing; Jin, Li; Teschendorff, Andrew E; Liu, Fan; Wang, Sijia.
Afiliação
  • Peng Q; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Liu X; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Li W; School of Future Technology, University of Chinese Academy of Sciences, Beijing, China.
  • Jing H; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Li J; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Gao X; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Luo Q; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Breeze CE; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Pan S; Altius Institute for Biomedical Sciences, Seattle, WA, USA.
  • Zheng Q; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Li G; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Qian J; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Yuan L; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Yuan N; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • You C; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Du S; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Zheng Y; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Yuan Z; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, and Human Phenome Institute, Fudan University, Shanghai, China.
  • Tan J; Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai, China.
  • Jia P; Taizhou Institute of Health Sciences, Fudan University, Taizhou, China.
  • Wang J; Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai, China.
  • Zhang G; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Lu X; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, and Human Phenome Institute, Fudan University, Shanghai, China.
  • Shi L; Taizhou Institute of Health Sciences, Fudan University, Taizhou, China.
  • Guo S; Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Shanghai, China.
  • Liu Y; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Ni T; Taizhou Institute of Health Sciences, Fudan University, Taizhou, China.
  • Wen B; Shenzhen Chipscreen Biosciences Co. Ltd., Shenzhen, China.
  • Zeng C; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, and Human Phenome Institute, Fudan University, Shanghai, China.
  • Jin L; Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai, China.
  • Teschendorff AE; Taizhou Institute of Health Sciences, Fudan University, Taizhou, China.
  • Liu F; Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
  • Wang S; Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI, USA.
Nat Genet ; 56(5): 846-860, 2024 May.
Article em En | MEDLINE | ID: mdl-38641644
ABSTRACT
Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Metilação de DNA / Locos de Características Quantitativas / População do Leste Asiático Limite: Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Metilação de DNA / Locos de Características Quantitativas / População do Leste Asiático Limite: Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China