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Alzheimer\u2019s disease (AD) is the most common neurodegenerative disorder, and several studies using the samples collected from Caucasian cohorts have found that epigenetics, particularly cytosine methylation, could play a role in the etiological process of AD. However, little research has been conducted using the samples of other ethnic groups. Here we generated genome-wide profiles of both 5mC and 5hmC in human frontal cortex tissues from late-onset Chinese AD patients and cognitively normal controls. We identified both Chinese-specific and overlapping differentially hydroxymethylated regions (DhMRs) with Caucasian cohorts. Pathway analyses revealed specific pathways enriched among Chinese-specific DhMRs, as well as the shared DhMRs with Caucasian cohorts. Furthermore, two important transcription factor-binding motifs, hypoxia-inducible factor 2\u03b1 (HIF2\u03b1) and hypoxia-inducible factor 1\u03b1 (HIF1\u03b1), were enriched in the DhMRs. Our analyses provide the first genome-wide profiling of DNA hydroxymethylation of the frontal cortex of AD patients from China, emphasizing an important role of 5hmC in AD pathogenesis and highlighting both ethnicity-specific and overlapping changes of brain hydroxymethylome in AD.<\/jats:p>","DOI":"10.1093\/hmg\/ddz273","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T20:09:37Z","timestamp":1573070977000},"page":"149-158","source":"Crossref","is-referenced-by-count":16,"title":["Ethnicity-specific and overlapping alterations of brain hydroxymethylome in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"29","author":[{"given":"Lixia","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"},{"name":"National Clinical Research Center for Geriatric Disorders (XIANGYA), Changsha, Hunan 410078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nannan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jifeng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"},{"name":"National Clinical Research Center for Geriatric Disorders (XIANGYA), Changsha, Hunan 410078, China"},{"name":"Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410008, China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"},{"name":"National Clinical Research Center for Geriatric Disorders (XIANGYA), Changsha, Hunan 410078, China"},{"name":"Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410008, China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily G","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiongwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-6659","authenticated-orcid":false,"given":"Peng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beisha","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"},{"name":"National Clinical Research Center for Geriatric Disorders (XIANGYA), Changsha, Hunan 410078, China"},{"name":"Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410008, China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 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