Comparison of DNA Methylation Profiles of Hemostatic Genes between Liver Tissue and Peripheral Blood within Individuals

Martina Olsson Lindvall; Annelie Angerfors; Björn Andersson; Staffan Nilsson; Marcela Davila Lopez; Lena Hansson; Tara M. Stanne; Christina Jern

doi:10.1055/s-0040-1720980

Thrombosis and Haemostasis, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Thromb Haemost 2021; 121(05): 573-583
DOI: 10.1055/s-0040-1720980

Coagulation and Fibrinolysis

Comparison of DNA Methylation Profiles of Hemostatic Genes between Liver Tissue and Peripheral Blood within Individuals

Martina Olsson Lindvall ^*

¹Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

²Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden

,

Annelie Angerfors‡^*

¹Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

³Bioinformatics Core Facility, University of Gothenburg, Gothenburg, Sweden

,

Björn Andersson

³Bioinformatics Core Facility, University of Gothenburg, Gothenburg, Sweden

,

Staffan Nilsson

¹Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

⁴Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden

,

Marcela Davila Lopez

³Bioinformatics Core Facility, University of Gothenburg, Gothenburg, Sweden

,

Lena Hansson

⁵NovoNordisk, Oxford, United Kingdom

,

Tara M. Stanne^**

¹Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

²Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden

,

Christina Jern^**

¹Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

²Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden

› Institutsangaben

Abstract

DNA methylation has become increasingly recognized in the etiology of complex diseases, including thrombotic disorders. Blood is often collected in epidemiological studies for genotyping and has recently also been used to examine DNA methylation in epigenome-wide association studies. DNA methylation patterns are often tissue-specific, thus, peripheral blood may not accurately reflect the methylation pattern in the tissue of relevance. Here, we collected paired liver and blood samples concurrently from 27 individuals undergoing liver surgery. We performed targeted bisulfite sequencing for a set of 35 hemostatic genes primarily expressed in liver to analyze DNA methylation levels of >10,000 cytosine-phosphate-guanine (CpG) dinucleotides. We evaluated whether DNA methylation in blood could serve as a proxy for DNA methylation in liver at individual CpGs. Approximately 30% of CpGs were nonvariable and were predominantly hypo- (<25%) or hypermethylated (>70%) in both tissues. While blood can serve as a proxy for liver at these CpGs, the low variability renders these unlikely to explain phenotypic differences. We therefore focused on CpG sites with variable methylation levels in liver. The level of blood–liver tissue correlation varied widely across these variable CpGs; moderate correlations (0.5 ≤ r < 0.75) were detected for 6% and strong correlations (r ≥ 0.75) for a further 4%. Our findings indicate that it is essential to study the concordance of DNA methylation between blood and liver at individual CpGs. This paired blood–liver dataset is intended as a resource to aid interpretation of blood-based DNA methylation results.

Keywords

DNA methylation - hemostasis - Factor VII - bisulfite sequencing - epigenetic

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