Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

Agha, Golareh; Mendelson, Michael; Ward‐Caviness, Cavin; Joehanes, Roby; Huan, Tian Xiao; Gondalia, Rahul; Salfati, Elias; Brody, Jennifer A.; Fiorito, Giovanni; Bressler, Jan; Chen, Brian H.; Ligthart, Symen; Guarrera, Simonetta; Colicino, Elena; Just, Allan C.; Wahl, Simone; Gieger, Christian; Vandiver, Amy R.; Tanaka, Toshiko; Hernandez, Dena G.; Pilling, Luke C.; Singleton, Andrew B.; Sacerdote, Carlotta; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Li, Yun; Zhang, Guosheng; Stewart, James D.; Floyd, James S.; Wiggins, Kerri L.; Rotter, Jerome I.; Multhaup, Michael; Bakulski, Kelly M.; Horvath, Steven; Tsao, Philip S.; Absher, Devin; Vokonas, Pantel; Hirschhorn, Joel N.; Fallin, M. Daniele; Liu, Chunyu; Bandinelli, Stefania; Boerwinkle, Eric; Dehghan, Abbas; Schwartz, Joel; Psaty, Bruce M.; Feinberg, Andrew P.; Hou, Lifang; Ferrucci, Luigi; Sotoodehnia, Nona; Matullo, Giuseppe; Peters, Annette; Fornage, Myriam; Assimes, Themistocles L.; Whitsel, Eric A.; Levy, Daniel; Baccarelli, Andrea A.

doi:10.1161/circulationaha.118.039357

Cited by 156 publications

(122 citation statements)

References 48 publications

(55 reference statements)

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“…Epigenetic signatures may display tissue specificity linked to disease mechanisms, however, obtaining kidney biopsy material is invasive and is not performed as part of routine clinical practice in people with DKD and T1D in the United Kingdom. Peripheral blood-based methylation biomarkers have shown promise in several clinical fields ( Moore et al, 2014 ; Agha et al, 2019 ; Cardenas et al, 2019 ; DiTroia et al, 2019 ; Henderson-Smith et al, 2019 ; Kerr et al, 2019a , b , 2020 ; Ladd-Acosta and Fallin, 2019 ; Zhou et al, 2019 ) including kidney disease ( Smyth et al, 2014b , 2018 ; Swan et al, 2015 ; Aranyi and Susztak, 2019 ; Gluck et al, 2019 ; Kato and Natarajan, 2019 ; Kerr et al, 2019b ; Park et al, 2019 ). We have previously demonstrated that blood-derived differential methylation is also reflected in kidney-derived differential methylation for CKD ( Smyth et al, 2014b ).…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

Smyth

Patterson

Swan

et al. 2020

Front. Cell Dev. Biol.

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A subset of individuals with type 1 diabetes will develop diabetic kidney disease (DKD). DKD is heritable and large-scale genome-wide association studies have begun to identify genetic factors that influence DKD. Complementary to genetic factors, we know that a person's epigenetic profile is also altered with DKD. This study reports analysis of DNA methylation, a major epigenetic feature, evaluating methylome-wide loci for association with DKD. Unique features (n = 485,577; 482,421 CpG probes) were evaluated in blood-derived DNA from carefully phenotyped White European individuals diagnosed with type 1 diabetes with (cases) or without (controls) DKD (n = 677 samples). Explicitly, 150 cases were compared to 100 controls using the 450K array, with subsequent analysis using data previously generated for a further 96 cases and 96 controls on the 27K array, and de novo methylation data generated for replication in 139 cases and 96 controls. Following stringent quality control, raw data were quantile normalized and beta values calculated to reflect the methylation status at each site. The difference in methylation status was evaluated between cases and controls; resultant P-values for array-based data were adjusted for multiple testing. Genes with significantly increased (hypermethylated) and/or decreased (hypomethylated) levels of DNA methylation were considered for biological relevance by functional enrichment analysis using KEGG pathways. Twenty-two loci demonstrated statistically significant fold changes associated with DKD and additional support for these associated loci was sought using independent samples derived from patients recruited with similar inclusion criteria. Markers associated with CCNL1 and ZNF187 genes are supported as differentially regulated loci (P < 10 −8), with evidence also presented for AFF3, which has been identified from a meta-analysis and subsequent replication of genomewide association studies. Further supporting evidence for differential gene expression in CCNL1 and ZNF187 is presented from kidney biopsy and blood-derived RNA in people with and without kidney disease from NephroSeq. Evidence confirming that methylation sites influence the development of DKD may aid risk prediction tools and stimulate research to identify epigenomic therapies which might be clinically useful for this disease.

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Section: Discussionmentioning

confidence: 99%

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

Smyth

Patterson

Swan

et al. 2020

Front. Cell Dev. Biol.

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“…In according to Golareh et al results [46], in order to evaluate the potential role of DNA methylation to predict CHD risk, we performed a predictive statistical model on…”

Section: Plos Onementioning

confidence: 99%

Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study

et al. 2020

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Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score = 0, uninjured coronaries and with no obstructive CHD (no critical stenosis, NCS) were considered as control subjects (n = 18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p = 0.05) of HLA-G gene in

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“…DNA methylation levels of colon samples were measured by 450 K Illumina Infinium HD Methylation Assay (Agha et al, 2019), which can access the methylation status of more than 450,000 CpG sites in the human genome. We first filtered out probes that had single nucleotide polymorphisms located in or close to the probe sequence.…”

Section: Methylation-gene Correlation Analysismentioning

confidence: 99%

Identification of Transcription Factor/Gene Axis in Colon Cancer Using a Methylome Approach

Zhang

Shen

et al. 2020

Front. Genet.

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Colon cancer is one of the most commonly diagnosed cancers worldwide. Both environmental and molecular characters can influence its development. DNA methylation has been heralded as a promising marker for use in cancer prevention, diagnosis, and treatment. It has been shown to facilitate cancer progression through multiple mechanisms. Changes in DNA methylation can inhibit or promote the binding of transcription factors (TFs) and further disturb gene regulation. Detection of DNA methylation-mediated regulatory events in colon cancer are critical for mining novel biomarkers. Here, we explore the influence of CpG sites located at promoter regions of differentially expressed genes and identify methylation-gene relationships using expression-methylation quantitative trait loci. We find that promoter methylation sites mainly negatively regulate the corresponding genes. We also identify candidate TFs that can bind to these sites in a sequence-dependent manner. By integrating transcriptome and methylome profiles, we construct a TF-CpG-gene regulatory network for colon cancer, which is used to determine the roles of TFs and methylation in the transcription process. Finally, based on TF-CpG-gene relationships, we design a framework to evaluate patient prognosis, which shows that one TF-CpG-gene triplet is significantly associated with patient survival rate and represents a potential novel biomarker for use in colon cancer prognosis and treatment.

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Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

Cited by 156 publications

References 48 publications

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study

Identification of Transcription Factor/Gene Axis in Colon Cancer Using a Methylome Approach

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