Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns
Joanna Ciantar,
Saara Marttila,
Sonja Rajić,
Daria Kostiniuk,
Pashupati P Mishra,
Leo-Pekka Lyytikäinen,
Nina Mononen,
Marcus E Kleber,
Winfried März,
Mika Kähönen,
Olli Raitakari,
Terho Lehtimäki,
Emma Raitoharju
Affiliations
Joanna Ciantar
Molecular Epidemiology (MOLE), Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Saara Marttila
Molecular Epidemiology (MOLE), Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Sonja Rajić
Molecular Epidemiology (MOLE), Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Daria Kostiniuk
Molecular Epidemiology (MOLE), Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Pashupati P Mishra
Department of Clinical Chemistry, Tays Research Services, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Leo-Pekka Lyytikäinen
Department of Clinical Chemistry, Tays Research Services, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Nina Mononen
Department of Clinical Chemistry, Tays Research Services, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Marcus E Kleber
Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, Heidelberg University, Mannheim, Germany
Winfried März
Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, Heidelberg University, Mannheim, Germany
Mika Kähönen
Department of Clinical Physiology, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Olli Raitakari
Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
Terho Lehtimäki
Department of Clinical Chemistry, Tays Research Services, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Emma Raitoharju
Molecular Epidemiology (MOLE), Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Eastern and Western Finns show a striking difference in coronary heart disease-related mortality; genetics is a known contributor for this discrepancy. Here, we discuss the potential role of DNA methylation in mediating the discrepancy in cardiometabolic disease-risk phenotypes between the sub-populations. We used data from the Young Finns Study (n = 969) to compare the genome-wide DNA methylation levels of East- and West-originating Finns. We identified 21 differentially methylated loci (FDR 2.5%) and 7 regions (smoothed FDR < 0.05; CpGs ≥ 5). Methylation at all loci and regions associates with genetic variants (p < 5 × 10−8). Independently of genetics, methylation at 11 loci and 4 regions associates with transcript expression, including genes encoding zinc finger proteins. Similarly, methylation at 5 loci and 4 regions associates with cardiometabolic disease-risk phenotypes including triglycerides, glucose, cholesterol, as well as insulin treatment. This analysis was also performed in LURIC (n = 2371), a German cardiovascular patient cohort, and results replicated for the association of methylation at cg26740318 and DMR_11p15 with diabetes-related phenotypes and methylation at DMR_22q13 with triglyceride levels. Our results indicate that DNA methylation differences between East and West Finns may have a functional role in mediating the cardiometabolic disease discrepancy between the sub-populations.
