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and technology program projects in Tibet Autonomous Region in 2017","award":["[2023] No.1"],"award-info":[{"award-number":["[2023] No.1"]}]},{"name":"The first batch of key science and technology program projects in Tibet Autonomous Region in 2017","award":["[2020] No.79"],"award-info":[{"award-number":["[2020] No.79"]}]},{"name":"The first batch of key science and technology program projects in Tibet Autonomous Region in 2017","award":["82241023"],"award-info":[{"award-number":["82241023"]}]},{"name":"Central Finance to Support the Development of Local Universities","award":["XZ202303ZY0008G"],"award-info":[{"award-number":["XZ202303ZY0008G"]}]},{"name":"Central Finance to Support the Development of Local Universities","award":["QYXTZX-RKZ2024-01-1"],"award-info":[{"award-number":["QYXTZX-RKZ2024-01-1"]}]},{"name":"Central Finance to Support the Development of Local Universities","award":["08080002"],"award-info":[{"award-number":["08080002"]}]},{"name":"Central Finance to Support the Development of Local Universities","award":["[2023] No.1"],"award-info":[{"award-number":["[2023] No.1"]}]},{"name":"Central Finance to Support the Development of Local Universities","award":["[2020] No.79"],"award-info":[{"award-number":["[2020] No.79"]}]},{"name":"Central Finance to Support the Development of Local Universities","award":["82241023"],"award-info":[{"award-number":["82241023"]}]},{"name":"National Science Foundation of China","award":["XZ202303ZY0008G"],"award-info":[{"award-number":["XZ202303ZY0008G"]}]},{"name":"National Science Foundation of China","award":["QYXTZX-RKZ2024-01-1"],"award-info":[{"award-number":["QYXTZX-RKZ2024-01-1"]}]},{"name":"National Science Foundation of China","award":["08080002"],"award-info":[{"award-number":["08080002"]}]},{"name":"National Science Foundation of China","award":["[2023] No.1"],"award-info":[{"award-number":["[2023] No.1"]}]},{"name":"National Science Foundation of China","award":["[2020] No.79"],"award-info":[{"award-number":["[2020] No.79"]}]},{"name":"National Science Foundation of China","award":["82241023"],"award-info":[{"award-number":["82241023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Repeated extreme environmental training (RET) enhances adaptability and induces lasting methylation modifications. We recruited 64 participants from a high-altitude region (4700 m), including 32 volunteers with repeated high-altitude exposure, reaching up to 8848 m and as many as 11 exposures. By analyzing 741,489 CpG loci and 39 phenotypes, we identified significant changes in 13 CpG loci (R2 &gt; 0.8, ACC &gt; 0.75) and 15 phenotypes correlated with increasing RET exposures. The phenotypic Bayesian causal network and phenotypic-CpG interaction networks showed greater robustness (node correlation) with more RET exposures, particularly in systolic blood pressure (SP), platelet count (PLT), and neutrophil count (NEUT). Six CpG sites were validated as significantly associated with hypoxia exposure using the GEO public da-taset (AltitudeOmics). Furthermore, dividing the participants into two groups based on the number of RET exposures (n = 9 and 4) revealed six CpG sites significantly corre-lated with PLT and red cell distribution width-standard deviation (RDW.SD). Our findings suggest that increased RET exposures strengthen the interactions between phenotypes and CpG sites, indicating that critical extreme adaptive states may alter methylation patterns, co-evolving with phenotypes such as PLT, RDW.SD, and NEUT.<\/jats:p>","DOI":"10.3390\/ijms252312652","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T08:38:24Z","timestamp":1732523904000},"page":"12652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["DNA Methylation Changes and Phenotypic Adaptations Induced Repeated Extreme Altitude Exposure at 8848 Meters"],"prefix":"10.3390","volume":"25","author":[{"given":"Shixuan","family":"Zhang","sequence":"first","affiliation":[{"name":"High Altitude Health Science Research Centre of Tibet University, Tibet University, 10 East Zangda Road, Lhasa 850000, China"},{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La","family":"Yang","sequence":"additional","affiliation":[{"name":"High Altitude Health Science Research Centre of Tibet University, Tibet University, 10 East Zangda Road, Lhasa 850000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoma","family":"Duoji","sequence":"additional","affiliation":[{"name":"High Altitude Health Science Research Centre of Tibet University, Tibet University, 10 East Zangda Road, Lhasa 850000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danzeng","family":"Qiangba","sequence":"additional","affiliation":[{"name":"High Altitude Health Science Research Centre of Tibet University, Tibet University, 10 East Zangda Road, Lhasa 850000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Hu","sequence":"additional","affiliation":[{"name":"Artificial Intelligence Innovation and Incubation Institute of Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoma","family":"Basang","sequence":"additional","affiliation":[{"name":"High Altitude Health Science Research Centre of Tibet University, Tibet University, 10 East Zangda Road, Lhasa 850000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s40279-017-0809-9","article-title":"The effect of natural or simulated altitude training on high-intensity intermittent running performance in team-sport athletes: A meta-analysis","volume":"48","author":"Hamlin","year":"2018","journal-title":"Sports Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1249\/00003677-198600140-00012","article-title":"Cardiovascular adaptation to exercise at high altitude","volume":"14","author":"Grover","year":"1986","journal-title":"Exerc. 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