Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns
Year: 2024
Type: article
Abstract: 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 < 0.05; Δβ >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.
Source: Epigenetics
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Estimated APC paid: $3,418
Funders: Foundation for Cardiovascular Research, Yrjö Jahnssonin Säätiö, European Commission, Kela, Academy of Finland, Bundesministerium für Bildung und Forschung, Suomen Kulttuurirahasto, Juho Vainion Säätiö, Signe ja Ane Gyllenbergin Säätiö, Emil Aaltosen Säätiö, Sydäntutkimussäätiö, Tampereen Tuberkuloosisäätiö, Diabetesliitto, Paavo Nurmen Säätiö, Tays, Syöpäsäätiö, European Research Council, Horizon 2020
Awards: G1000894810, G1037428335, G1255523522, G1601895641, G1686171937, G1763104746, G1872575776, Kompetenzcluster Ernährungsforschung: nutriCARD 'Kompetenzcluster für Ernährung und kardiovaskuläre Gesundheit, Universität Jena - 2. Förderphase', G2330237237, G234837756, G247187792, G2513778610, A high-dimensional approach for unwinding immune-metabolic causes of cardiovascular disease-depression multimorbidities, G3213590351, G33539551, G3582688621, G3858258543, G4351223834, G4530067370, G4655867613, Kompetenzcluster Ernährungsforschung: nutriCARD 'Kompetenzcluster für Ernährung und kardiovaskuläre Gesundheit, Universität Jena', G4965406020, G5090981026, G5208171454, G523551622, G5474452856, G5512925732, G6164432047, G6310393984, G692875121, G69797456, Lifelong and transgenerational epigenetic profiles in relation to the development of cardiometabolic diseases, G8950285126
OpenAlex ID: W4402102248