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Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns

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-popul...

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Main Authors: Ciantar, Joanna (Author) , Marttila, Saara (Author) , Rajić, Sonja (Author) , Kostiniuk, Daria (Author) , Mishra, Pashupati P (Author) , Lyytikäinen, Leo-Pekka (Author) , Mononen, Nina (Author) , Kleber, Marcus E. (Author) , März, Winfried (Author) , Kähönen, Mika (Author) , Raitakari, Olli (Author) , Lehtimäki, Terho (Author) , Raitoharju, Emma (Author)
Format: Article (Journal)
Language:English
Published: 01 Sep 2024
In: Epigenetics
Year: 2024, Volume: 19, Issue: 1, Pages: 1-19
ISSN:1559-2308
DOI:10.1080/15592294.2024.2397297
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1080/15592294.2024.2397297
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Author Notes: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, and Emma Raitoharju
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Summary: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.
Item Description:Online veröffentlicht: 01. September 2024
Gesehen am 17.10.2024
Physical Description:Online Resource
ISSN:1559-2308
DOI:10.1080/15592294.2024.2397297

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