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

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-09-01 DOI:10.1080/15592294.2024.2397297
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
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引用次数: 0

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.

东西方芬兰人 DNA 甲基化差异的鉴定和功能特征。
东部和西部芬兰人在冠心病相关死亡率方面存在显著差异;众所周知,遗传是造成这种差异的原因之一。在此,我们讨论了 DNA 甲基化在介导亚人群之间心脏代谢疾病风险表型差异方面的潜在作用。我们利用年轻芬兰人研究(n = 969)的数据,比较了东西方芬兰人的全基因组 DNA 甲基化水平。我们发现了 21 个差异甲基化位点(FDR < 0.05;Δβ >2.5%)和 7 个区域(平滑 FDR p -8)。与遗传无关,11 个位点和 4 个区域的甲基化与转录本表达有关,包括编码锌指蛋白的基因。同样,5 个基因位点和 4 个区域的甲基化与心脏代谢疾病风险表型有关,包括甘油三酯、葡萄糖、胆固醇以及胰岛素治疗。这项分析也在德国心血管病人队列 LURIC(n = 2371)中进行,结果证实了 cg26740318 和 DMR_11p15 的甲基化与糖尿病相关表型的关系,以及 DMR_22q13 的甲基化与甘油三酯水平的关系。我们的研究结果表明,东西芬兰人之间的 DNA 甲基化差异可能在介导亚人群之间的心脏代谢疾病差异方面发挥了功能性作用。
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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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