Whole-Genome Differentially Hydroxymethylated DNA Regions among Twins Discordant for Cardiovascular Death

Genes

卷:12

Han-Tian Guo¹  Ruth E. Krasnow²  Zhongming Zhao³  Thomas J. Wang⁴  Terry Reed⁵  Jun Dai⁶  Wael El-Rifai⁷  Weihua Guan⁸  Ming Leung⁹ 

[1] Bioinformatics and Computational Biology Undergraduate Program, Iowa State University, Ames, IA 50011, USA;

[2] Center for Health Sciences, SRI International, Menlo Park, CA 94025, USA;

[3] Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA;

[4] Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;

[5] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA;

[6] Department of Public Health, College of Health Sciences, Des Moines University, Des Moines, IA 50312, USA;

[7] Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA;

[8] Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA;

[9] Institute for Personalized Medicine, Penn State College of Medicine, Hershey, PA 17033, USA;

关键词: hydroxymethylation;    twins;    monozygotic;    dizygotic;    cardiovascular disease;   

DOI  :  10.3390/genes12081183

来源: DOAJ

【 摘 要 】

Epigenetics is a mechanism underlying cardiovascular disease. It is unknown whether DNA hydroxymethylation is prospectively associated with the risk for cardiovascular death independent of germline and common environment. Male twin pairs middle-aged in 1969–1973 and discordant for cardiovascular death through December 31, 2014, were included. Hydroxymethylation was quantified in buffy coat DNA collected in 1986–1987. The 1893 differentially hydroxymethylated regions (DhMRs) were identified after controlling for blood leukocyte subtypes and age among 12 monozygotic (MZ) pairs (Benjamini–Hochberg False Discovery Rate < 0.01), of which the 102 DhMRs were confirmed with directionally consistent log₂-fold changes and p < 0.01 among additional 7 MZ pairs. These signature 102 DhMRs, independent of the germline, were located on all chromosomes except for chromosome 21 and the Y chromosome, mainly within/overlapped with intergenic regions and introns, and predominantly hyper-hydroxymethylated. A binary linear classifier predicting cardiovascular death among 19 dizygotic pairs was identified and equivalent to that generated from MZ via the 2D transformation. Computational bioinformatics discovered pathways, phenotypes, and DNA motifs for these DhMRs or their subtypes, suggesting that hydroxymethylation was a pathophysiological mechanism underlying cardiovascular death that might be influenced by genetic factors and warranted further investigations of mechanisms of these signature regions in vivo and in vitro.

【 授权许可】

Unknown