1. Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns.
- Author
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Ciantar J, Marttila S, Rajić S, Kostiniuk D, Mishra PP, Lyytikäinen LP, Mononen N, Kleber ME, März W, Kähönen M, Raitakari O, Lehtimäki T, and Raitoharju E
- Subjects
- Humans, Finland, Male, Female, Adult, CpG Islands, Middle Aged, Genome-Wide Association Study, DNA Methylation
- 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.- Published
- 2024
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