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Cardiovascular epigenetics

Section information

The impact of epigenetics in cardiovascular disease is now emerging as an important player at different levels from etiology to therapeutics. This section publishes original epigenetic research and reviews in all cardiovascular medical specialties from both animal model and human studies. Research that links epigenetic regulation with cardiovascular risk factors, biomarkers and subclinical cardiovascular diseases will also be included in this section.

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  1. Cardiovascular health (CVH) was defined by the American Heart Association as an integrative idealness of seven clinical or lifestyle factors. Based on populations of European ancestry, recent studies have show...

    Authors: Yun-Hsiang Lo and Wan-Yu Lin
    Citation: Clinical Epigenetics 2022 14:73
    Content type: Research Published on:

  2. Acute myocardial infarction (AMI) has been one of the most fatal diseases among all types of heart diseases due to its rapid onset and high rates of fatality. Understanding accurately how multi-omics molecular...

    Authors: Xiaoli Luo, Yi Hu, Junwei Shen, Xinwen Liu, Tao Wang, Li Li and Jue Li
    Citation: Clinical Epigenetics 2022 14:46
    Content type: Research Published on:

  3. This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature.

    Authors: Denis Seyres, Alessandra Cabassi, John J. Lambourne, Frances Burden, Samantha Farrow, Harriet McKinney, Joana Batista, Carly Kempster, Maik Pietzner, Oliver Slingsby, Thong Huy Cao, Paulene A. Quinn, Luca Stefanucci, Matthew C. Sims, Karola Rehnstrom, Claire L. Adams…
    Citation: Clinical Epigenetics 2022 14:39
    Content type: Research Published on:

  4. Recent studies have suggested that folic acid can restore abnormal DNA methylation and monocyte subset shifts caused by hyperhomocysteinemia (HHcy) and hyperlipidemia (HL). However, the exact mechanism of acti...

    Authors: Yang Xiang, Bin Liang, Xiaokang Zhang, Xueping Qiu, Qianyun Deng, Li Yu, Hong Yu, Zhibing Lu and Fang Zheng
    Citation: Clinical Epigenetics 2022 14:32
    Content type: Research Published on:

  5. GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with atherosclerotic cardiovascular disease. However, the associations between early adulthood lipid levels and...

    Authors: Tao Gao, John T. Wilkins, Yinan Zheng, Brian T. Joyce, David R. Jacobs Jr., Pamela J. Schreiner, Steve Horvath, Philip Greenland, Donald Lloyd-Jones and Lifang Hou
    Citation: Clinical Epigenetics 2022 14:16
    Content type: Research Published on:

  6. Heart failure with preserved ejection fraction (HFpEF), affected collectively by genetic and environmental factors, is the common subtype of chronic heart failure. Although the available risk assessment method...

    Authors: Xuetong Zhao, Yang Sui, Xiuyan Ruan, Xinyue Wang, Kunlun He, Wei Dong, Hongzhu Qu and Xiangdong Fang
    Citation: Clinical Epigenetics 2022 14:11
    Content type: Research Published on:

  7. DNA methylation, an epigenetic mechanism modulated by lifestyle and environmental factors, may be an important biomarker of complex diseases including cardiovascular diseases (CVD) and subclinical atherosclero...

    Authors: Farah Ammous, Wei Zhao, Lisha Lin, Scott M. Ratliff, Thomas H. Mosley, Lawrence F. Bielak, Xiang Zhou, Patricia A. Peyser, Sharon L. R. Kardia and Jennifer A. Smith
    Citation: Clinical Epigenetics 2022 14:10
    Content type: Research Published on:

  8. The prevalence of cardiometabolic disease (CMD) is rising globally, with environmentally induced epigenetic changes suggested to play a role. Few studies have investigated epigenetic associations with CMD risk...

    Authors: Elie Antoun, Prachand Issarapu, Chiara di Gravio, Smeeta Shrestha, Modupeh Betts, Ayden Saffari, Sirazul A. Sahariah, Alagu Sankareswaran, Manisha Arumalla, Andrew M. Prentice, Caroline H. D. Fall, Matt J. Silver, Giriraj R. Chandak and Karen A. Lillycrop
    Citation: Clinical Epigenetics 2022 14:6
    Content type: Research Published on:

  9. Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at ide...

    Authors: Mitzi M. van Andel, Maarten Groenink, Maarten P. van den Berg, Janneke Timmermans, Arthur J. H. A. Scholte, Barbara J. M. Mulder, Aeilko H. Zwinderman and Vivian de Waard
    Citation: Clinical Epigenetics 2021 13:217
    Content type: Research Published on:

  11. Atherosclerotic plaque vulnerability is a key feature of atheroprogression and precipitating acute cardiovascular events. Although the pivotal role of epigenetic regulation in atherosclerotic plaque destabiliz...

    Authors: Jingjin Li, Xiaoping Zhang, Mengxi Yang, Hang Yang, Ning Xu, Xueqiang Fan, Gang Liu, Xintong Jiang, Jiasai Fan, Lifang Zhang, Hu Zhang, Ying Zhou, Rui Li, Si Gao, Jiangli Jin, Zening Jin…
    Citation: Clinical Epigenetics 2021 13:161
    Content type: Research Published on:

  12. Mutations in LMNA, encoding lamin A/C, lead to a variety of diseases known as laminopathies including dilated cardiomyopathy (DCM) and skeletal abnormalities. Though previous studies have investigated the dysregu...

    Authors: Julien L. P. Morival, Halida P. Widyastuti, Cecilia H. H. Nguyen, Michael V. Zaragoza and Timothy L. Downing
    Citation: Clinical Epigenetics 2021 13:139
    Content type: Research Published on:

  14. Thoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examin...

    Authors: Peiru Liu, Jing Zhang, Duo Du, Dandan Zhang, Zelin Jin, Wenqing Qiu, Xiushi Zhou, Shulong Dong, Mengyu Zhou, Heyu Zhao, Wei Zhang, Jiakang Ma, Shaoyang Sun, Weiguo Fu, Yun Liu and Lixin Wang
    Citation: Clinical Epigenetics 2021 13:124
    Content type: Research Published on:

  16. The epigenetic landscape underlying cardiovascular disease (CVD) is not completely understood and the clinical value of the identified biomarkers is still limited. We aimed to identify differentially methylate...

    Authors: Alba Fernández-Sanlés, Sergi Sayols-Baixeras, Isaac Subirana, Mariano Sentí, S. Pérez-Fernández, Manuel de Castro Moura, Manel Esteller, Jaume Marrugat and Roberto Elosua
    Citation: Clinical Epigenetics 2021 13:86
    Content type: Research Published on:

  17. The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets....

    Authors: Guillermo Palou-Márquez, Isaac Subirana, Lara Nonell, Alba Fernández-Sanlés and Roberto Elosua
    Citation: Clinical Epigenetics 2021 13:75
    Content type: Research Published on:

  18. Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causin...

    Authors: J. Pei, M. Schuldt, E. Nagyova, Z. Gu, S. el Bouhaddani, L. Yiangou, M. Jansen, J. J. A. Calis, L. M. Dorsch, C. Snijders Blok, N. A. M. van den Dungen, N. Lansu, B. J. Boukens, I. R. Efimov, M. Michels, M. C. Verhaar…
    Citation: Clinical Epigenetics 2021 13:61
    Content type: Research Published on:

  19. Cardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers fo...

    Authors: Farah Ammous, Wei Zhao, Scott M. Ratliff, Thomas H. Mosley, Lawrence F. Bielak, Xiang Zhou, Patricia A. Peyser, Sharon L. R. Kardia and Jennifer A. Smith
    Citation: Clinical Epigenetics 2021 13:55
    Content type: Research Published on:

  20. Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom...

    Authors: Tess D. Pottinger, Sadiya S. Khan, Yinan Zheng, Wei Zhang, Hilary A. Tindle, Matthew Allison, Gretchen Wells, Aladdin H. Shadyab, Rami Nassir, Lisa Warsinger Martin, JoAnn E. Manson, Donald M. Lloyd-Jones, Philip Greenland, Andrea A. Baccarelli, Eric A. Whitsel and Lifang Hou
    Citation: Clinical Epigenetics 2021 13:42
    Content type: Research Published on:

  21. Dilated cardiomyopathy (DCM) is a serious cardiac heterogeneous pathological disease, which may be caused by mutations in the LMNA gene. Lamins interact with not only lamina-associated domains (LADs) but also ...

    Authors: Xiaolin Zhang, Xiuli Shao, Ruijia Zhang, Rongli Zhu and Rui Feng
    Citation: Clinical Epigenetics 2021 13:3
    Content type: Research Published on:

  22. Patients with cardiovascular disease (CVD) and type 2 diabetes (DM2) have a high residual risk for experiencing a major adverse cardiac event. Dysregulation of epigenetic mechanisms of gene transcription in in...

    Authors: Sylwia Wasiak, Kim E. Dzobo, Brooke D. Rakai, Yannick Kaiser, Miranda Versloot, Mahnoush Bahjat, Stephanie C. Stotz, Li Fu, Michael Sweeney, Jan O. Johansson, Norman C. W. Wong, Erik S. G. Stroes, Jeffrey Kroon and Ewelina Kulikowski
    Citation: Clinical Epigenetics 2020 12:166
    Content type: Research Published on:

  23. Tobacco smoking is a well-known modifiable risk factor for many chronic diseases, including cardiovascular disease (CVD). One of the proposed underlying mechanism linking smoking to disease is via epigenetic m...

    Authors: Silvana C. E. Maas, Michelle M. J. Mens, Brigitte Kühnel, Joyce B. J. van Meurs, André G. Uitterlinden, Annette Peters, Holger Prokisch, Christian Herder, Harald Grallert, Sonja Kunze, Melanie Waldenberger, Maryam Kavousi, Manfred Kayser and Mohsen Ghanbari
    Citation: Clinical Epigenetics 2020 12:157
    Content type: Research Published on:

  24. Atrial natriuretic peptide (ANP), one of the main members of the natriuretic peptides system, has been associated with hypertension and related complications, but the underlying molecular mechanisms are not ve...

    Authors: Jing Li, Jinhua Zhu, Liyun Ren, Shengqi Ma, Bin Shen, Jia Yu, Rongyan Zhang, Mingzhi Zhang, Yan He and Hao Peng
    Citation: Clinical Epigenetics 2020 12:133
    Content type: Research Published on:

  25. H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigate...

    Authors: Jiayi Pei, Magdalena Harakalova, Thomas A. Treibel, R Thomas Lumbers, Bastiaan J. Boukens, Igor R. Efimov, Jip T. van Dinter, Arantxa González, Begoña López, Hamid El Azzouzi, Noortje van den Dungen, Christian G. M. van Dijk, Merle M. Krebber, Hester M. den Ruijter, Gerard Pasterkamp, Dirk J. Duncker…
    Citation: Clinical Epigenetics 2020 12:106
    Content type: Research Published on:

  26. Atherosclerosis is the main cause of cardiovascular diseases such as ischemic stroke and coronary heart disease. Gene-specific promoter methylation changes have been suggested as one of the causes underlying t...

    Authors: Jee Yeon Kim, Bong-Geun Choi, Jaroslav Jelinek, Dae Hyun Kim, Seo Hyun Lee, Kwangjo Cho, Seo Hee Rha, Young Ho Lee, Hyo Sun Jin, Dae-Kyoung Choi, Geun-Eun Kim, Sun U. Kwon, Junha Hwang, Jae Kwan Cha, Sukhoon Lee, Jean-Pierre J. Issa…
    Citation: Clinical Epigenetics 2020 12:66
    Content type: Research Published on:

  27. Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical va...

    Authors: Edwina H. Yeung, Weihua Guan, Xuehuo Zeng, Lucas A. Salas, Sunni L. Mumford, Paula de Prado Bert, Evelien R. van Meel, Anni Malmberg, Jordi Sunyer, Liesbeth Duijts, Janine F. Felix, Darina Czamara, Esa Hämäläinen, Elisabeth B. Binder, Katri Räikkönen, Jari Lahti…
    Citation: Clinical Epigenetics 2020 12:60
    Content type: Research Published on:

  28. DNA methylation is associated with body mass index (BMI), but it is not clear if methylation scores are biomarkers for extant BMI or predictive of future BMI. Here, we explore the causal nature and predictive ...

    Authors: Zoe E. Reed, Matthew J. Suderman, Caroline L. Relton, Oliver S. P. Davis and Gibran Hemani
    Citation: Clinical Epigenetics 2020 12:50
    Content type: Research Published on:

  29. The vasculature not only transports oxygenated blood, metabolites, and waste products but also serves as a conduit for hormonal communication between distant tissues. Therefore, it is important to maintain hom...

    Authors: Xiang Wei, Xin Yi, Xue-Hai Zhu and Ding-Sheng Jiang
    Citation: Clinical Epigenetics 2020 12:30
    Content type: Review Published on:

  30. The association between obesity and cardiovascular disease (CVD) is proven, but why some adults with obesity develop CVD while others remain disease-free is poorly understood. Here, we investigated whether mit...

    Authors: Sarah Corsi, Simona Iodice, Luisella Vigna, Akin Cayir, John C. Mathers, Valentina Bollati and Hyang-Min Byun
    Citation: Clinical Epigenetics 2020 12:29
    Content type: Research Published on:

  31. The 5-hydroxymethylcytosine (5hmC) DNA modification is an epigenetic marker involved in a range of biological processes. Its function has been studied extensively in tumors, neurodegenerative diseases, and ath...

    Authors: Chaoran Dong, Jiemei Chen, Jilin Zheng, Yiming Liang, Tao Yu, Yupeng Liu, Feng Gao, Jie Long, Hangyu Chen, Qianhui Zhu, Zilong He, Songnian Hu, Chuan He, Jian Lin, Yida Tang and Haibo Zhu
    Citation: Clinical Epigenetics 2020 12:17
    Content type: Research Published on:

  32. Identifying subjects with a high risk of ischemic stroke is fundamental for prevention of the disease. Both genetic and environmental risk factors contribute to ischemic stroke, but the underlying epigenetic m...

    Authors: Xueying Qin, Jin Li, Tao Wu, Yiqun Wu, Xun Tang, Pei Gao, Lin Li, Mengying Wang, Yao Wu, Xiaowen Wang, Dafang Chen and Yonghua Hu
    Citation: Clinical Epigenetics 2019 11:189
    Content type: Research Published on:

  33. Platelet-endothelial aggregation receptor 1 (PEAR-1) is a transmembrane receptor involved in platelet activation and megakaryopoiesis whose expression is driven by DNA methylation. PEAR1 variants were associated ...

    Authors: Benedetta Izzi, Francesco Gianfagna, Wen-Yi Yang, Katrien Cludts, Amalia De Curtis, Peter Verhamme, Augusto Di Castelnuovo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Jan A. Staessen, Marc F. Hoylaerts and Licia Iacoviello
    Citation: Clinical Epigenetics 2019 11:151
    Content type: Research Published on:

  34. Epigenome-wide association studies using DNA methylation have the potential to uncover novel biomarkers and mechanisms of cardiovascular disease (CVD) risk. However, the direction of causation for these associ...

    Authors: Kenneth Westerman, Paola Sebastiani, Paul Jacques, Simin Liu, Dawn DeMeo and José M. Ordovás
    Citation: Clinical Epigenetics 2019 11:142
    Content type: Research Published on:

  36. Apabetalone (RVX-208) is a bromodomain and extraterminal protein inhibitor (BETi) that in phase II trials reduced the relative risk (RR) of major adverse cardiac events (MACE) in patients with cardiovascular d...

    Authors: Laura M. Tsujikawa, Li Fu, Shovon Das, Christopher Halliday, Brooke D. Rakai, Stephanie C. Stotz, Christopher D. Sarsons, Dean Gilham, Emily Daze, Sylwia Wasiak, Deborah Studer, Kristina D. Rinker, Michael Sweeney, Jan O. Johansson, Norman C. W. Wong and Ewelina Kulikowski
    Citation: Clinical Epigenetics 2019 11:102
    Content type: Research Published on:

  37. Cardiac disease modelling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) requires thorough insight into cardiac cell type differentiation processes. However, current methods to dis...

    Authors: Kirstin Hoff, Marta Lemme, Anne-Karin Kahlert, Kerstin Runde, Enrique Audain, Dorit Schuster, Jens Scheewe, Tim Attmann, Thomas Pickardt, Almuth Caliebe, Reiner Siebert, Hans-Heiner Kramer, Hendrik Milting, Arne Hansen, Ole Ammerpohl and Marc-Phillip Hitz
    Citation: Clinical Epigenetics 2019 11:89
    Content type: Research Published on:

  38. Hypertension is one of primary clinical presentations of pre-eclampsia. The occurrence and progress of hypertension are closely related to vascular dysfunction. However, information is limited regarding the pa...

    Authors: Qinqin Gao, Xiaorong Fan, Ting Xu, Huan Li, Yun He, Yuxian Yang, Jie Chen, Hongmei Ding, Jianying Tao and Zhice Xu
    Citation: Clinical Epigenetics 2019 11:84
    Content type: Research Published on:

  39. Zinc finger and BTB domain-containing protein 12 (ZBTB12) is a predicted transcription factor with potential role in hematopoietic development. Recent evidence linked low methylation level of ZBTB12 exon1 to myoc...

    Authors: Fabrizia Noro, Francesco Gianfagna, Alessandro Gialluisi, Amalia De Curtis, Augusto Di Castelnuovo, Emanuela Napoleone, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Marc F. Hoylaerts, Licia Iacoviello and Benedetta Izzi
    Citation: Clinical Epigenetics 2019 11:74
    Content type: Research Published on:

  40. Toll-like receptor 4 (TLR4) expression is increased in activated monocytes, which play a critical role in the pathogenesis of coronary artery disease (CAD). However, the mechanism remains unclear. Regulatory f...

    Authors: Pei Du, Keqin Gao, Yu Cao, Shuang Yang, Yang Wang, Ren Guo, Ming Zhao and Sujie Jia
    Citation: Clinical Epigenetics 2019 11:44
    Content type: Research Published on:

  41. Patients with unprovoked first venous thromboembolism (VTE) are at a high risk of recurrence. Although circulating microRNAs (miRNAs) have been found to be associated with VTE and are markers of hypercoagulabi...

    Authors: Xiao Wang, Kristina Sundquist, Peter J. Svensson, Hamideh Rastkhani, Karolina Palmér, Ashfaque A. Memon, Jan Sundquist and Bengt Zöller
    Citation: Clinical Epigenetics 2019 11:28
    Content type: Research Published on:

  42. Most research into myocardial infarctions (MIs) have focused on preventative efforts. For survivors, the occurrence of an MI represents a major clinical event that can have long-lasting consequences. There has...

    Authors: Cavin K. Ward-Caviness, Golareh Agha, Brian H. Chen, Liliane Pfeiffer, Rory Wilson, Petra Wolf, Christian Gieger, Joel Schwartz, Pantel S. Vokonas, Lifang Hou, Allan C. Just, Stefania Bandinelli, Dena G. Hernandez, Andrew B. Singleton, Holger Prokisch, Thomas Meitinger…
    Citation: Clinical Epigenetics 2018 10:161
    Content type: Research Published on:

  43. Recently, epigenetic age acceleration—or older epigenetic age in comparison to chronological age—has been robustly associated with mortality and various morbidities. However, accelerated epigenetic aging has n...

    Authors: Marguerite R. Irvin, Stella Aslibekyan, Anh Do, Degui Zhi, Bertha Hidalgo, Steven A. Claas, Vinodh Srinivasasainagendra, Steve Horvath, Hemant K. Tiwari, Devin M. Absher and Donna K. Arnett
    Citation: Clinical Epigenetics 2018 10:56
    Content type: Research Published on:

  44. The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constit...

    Authors: Tomi Akinyemiju, Anh N. Do, Amit Patki, Stella Aslibekyan, Degui Zhi, Bertha Hidalgo, Hemant K. Tiwari, Devin Absher, Xin Geng, Donna K. Arnett and Marguerite R. Irvin
    Citation: Clinical Epigenetics 2018 10:49
    Content type: Research Published on:

  45. Early pulmonary oxygen exposure is one of the most important factors implicated in the development of bronchopulmonary dysplasia (BPD).

    Authors: Cho-Ming Chao, Rhea van den Bruck, Samantha Lork, Janica Merkle, Laura Krampen, Patrick P Weil, Malik Aydin, Saverio Bellusci, Andreas C. Jenke and Jan Postberg
    Citation: Clinical Epigenetics 2018 10:37
    Content type: Research Published on:

  46. Alterations in DNA methylation are demonstrated in atherosclerosis pathogenesis. However, changing rules of global DNA methylation and hydroxymethylation in peripheral blood leukocytes (PBLs) and different blo...

    Authors: Qianyun Deng, Wei Huang, Chunyan Peng, Jiajia Gao, Zuhua Li, Xueping Qiu, Na Yang, Bifeng Yuan and Fang Zheng
    Citation: Clinical Epigenetics 2018 10:9
    Content type: Research Published on:

  47. Aortic valve stenosis is the most common cardiac valve disease, and with current trends in the population demographics, its prevalence is likely to rise, thus posing a major health and economic burden facing t...

    Authors: Igor Gošev, Martina Zeljko, Željko Đurić, Ivana Nikolić, Milorad Gošev, Sanja Ivčević, Dino Bešić, Zoran Legčević and Frane Paić
    Citation: Clinical Epigenetics 2017 9:106
    Content type: Review Published on:

  48. Excess adiposity in childhood is associated with numerous adverse health outcomes. As this condition is difficult to treat once present, identification of risk early in life can help inform and implement strat...

    Authors: Jacob K. Kresovich, Yinan Zheng, Andres Cardenas, Brian T. Joyce, Sheryl L. Rifas-Shiman, Emily Oken, Matthew W. Gillman, Marie-France Hivert, Andrea A. Baccarelli and Lifang Hou
    Citation: Clinical Epigenetics 2017 9:86
    Content type: Research Published on:

  49. Development of cardiovascular disease (CVD), including coronary artery disease, arrhythmia, and ischemic stroke, depends on environmental and genetic factors. To investigate the epigenetic basis of myocardial ...

    Authors: Masahiro Nakatochi, Sahoko Ichihara, Ken Yamamoto, Keiko Naruse, Shigeki Yokota, Hiroyuki Asano, Tatsuaki Matsubara and Mitsuhiro Yokota
    Citation: Clinical Epigenetics 2017 9:54
    Content type: Short report Published on:

  50. DNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of trig...

    Authors: Kim V. E. Braun, Klodian Dhana, Paul S. de Vries, Trudy Voortman, Joyce B. J. van Meurs, Andre G. Uitterlinden, Albert Hofman, Frank B. Hu, Oscar H. Franco and Abbas Dehghan
    Citation: Clinical Epigenetics 2017 9:15
    Content type: Research Published on:

Clinical Epigenetics

ISSN: 1868-7083

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