Hubers Nikki, Drouard Gabin, Jansen Rick, Pool René, Hottenga Jouke Jan, Ollikainen Miina, Wang Xiaoling, Willemsen Gonneke, Kaprio Jaakko, Boomsma Dorret I, van Dongen Jenny
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Amsterdam Reproduction & Development (AR&D) Research Institute, Amsterdam, The Netherlands.
Am J Med Genet A. 2025 Apr;197(4):e63971. doi: 10.1002/ajmg.a.63971. Epub 2024 Dec 16.
Monozygotic (MZ) and dizygotic (DZ) twins are studied to understand genetic and environmental influences on complex traits, however the mechanisms behind twinning are not completely understood. (Epi)genomic studies identified SNPs associated with DZ twinning and DNA methylation sites with MZ twinning. To find molecular biomarkers of twinning, we compared transcriptomics and metabolomics data from MZ and DZ twins. We analyzed 42,663 RNA transcripts in 1453 MZ twins and 1294 DZ twins from the Netherlands Twin Register (NTR), followed by sex-stratified analyses. The top 5% transcripts with lowest p-values were analyzed for replication in 217 MZ and 158 DZ twins from the older Finnish Twin cohort (FTC). In the NTR, one transcript (PURG) was significantly differentially expressed between MZ and DZ twins; but this did not replicate in FTC. Pathway analyses highlighted the WNT-pathway, previously associated with MZ twinning, and the TGF-B and SMAD pathway, previously associated with DZ twinning. Meta-analysis of 169 serum metabolites in 2797 MZ and 2040 DZ twins from the NTR, FTC and FinnTwin12, showed no metabolomic differences. Overall, we did not find replicable transcript-level expression differences in blood between MZ and DZ twins, but highlighted the TGF-B/SMAD pathway as a potential transcriptional biomarker for DZ twinning.
对同卵双胞胎（MZ）和异卵双胞胎（DZ）进行研究，以了解遗传和环境对复杂性状的影响，然而双胞胎形成背后的机制尚未完全明了。（表观）基因组学研究确定了与异卵双胞胎相关的单核苷酸多态性（SNP）以及与同卵双胞胎相关的DNA甲基化位点。为了找到双胞胎的分子生物标志物，我们比较了同卵双胞胎和异卵双胞胎的转录组学和代谢组学数据。我们分析了来自荷兰双胞胎登记处（NTR）的1453对同卵双胞胎和1294对异卵双胞胎的42,663个RNA转录本，随后进行了性别分层分析。对p值最低的前5%转录本在来自芬兰双胞胎队列（FTC）的217对同卵双胞胎和158对异卵双胞胎中进行了重复分析。在NTR中，一个转录本（PURG）在同卵双胞胎和异卵双胞胎之间存在显著差异表达；但在FTC中未得到重复验证。通路分析突出了先前与同卵双胞胎相关的WNT通路，以及先前与异卵双胞胎相关的TGF-B和SMAD通路。对来自NTR、FTC和芬兰双胞胎12队列的2797对同卵双胞胎和2040对异卵双胞胎的169种血清代谢物进行的荟萃分析显示，代谢组学上没有差异。总体而言，我们未在同卵双胞胎和异卵双胞胎的血液中发现可重复的转录水平表达差异，但强调TGF-B/SMAD通路作为异卵双胞胎潜在的转录生物标志物。
