Transcriptomic and Metabolomic Analyses in Monozygotic and Dizygotic Twins.

IF 1.7 4区生物学 Q3 GENETICS & HEREDITY

American Journal of Medical Genetics Part A Pub Date : 2024-12-16 DOI:10.1002/ajmg.a.63971

Nikki Hubers, Gabin Drouard, Rick Jansen, René Pool, Jouke Jan Hottenga, Miina Ollikainen, Xiaoling Wang, Gonneke Willemsen, Jaakko Kaprio, Dorret I Boomsma, Jenny van Dongen

{"title":"Transcriptomic and Metabolomic Analyses in Monozygotic and Dizygotic Twins.","authors":"Nikki Hubers, Gabin Drouard, Rick Jansen, René Pool, Jouke Jan Hottenga, Miina Ollikainen, Xiaoling Wang, Gonneke Willemsen, Jaakko Kaprio, Dorret I Boomsma, Jenny van Dongen","doi":"10.1002/ajmg.a.63971","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63971"},"PeriodicalIF":1.7000,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Medical Genetics Part A","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/ajmg.a.63971","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

单卵双胞胎和异卵双胞胎的转录组和代谢组分析

研究单卵（MZ）双胞胎和双卵（DZ）双胞胎是为了了解遗传和环境对复杂性状的影响，但对孪生背后的机制还不完全清楚。(外显子）基因组研究发现了与 DZ 双胞胎相关的 SNPs 和与 MZ 双胞胎相关的 DNA 甲基化位点。为了找到孪生的分子生物标志物，我们比较了来自 MZ 和 DZ 双胞胎的转录组学和代谢组学数据。我们分析了荷兰双胞胎登记册（NTR）中1453对MZ双胞胎和1294对DZ双胞胎的42663个RNA转录本，然后进行了性别分层分析。在较早的芬兰双胞胎队列（FTC）中，对 217 对 MZ 双胞胎和 158 对 DZ 双胞胎中 p 值最低的前 5%转录本进行了复制分析。在 NTR 中，有一个转录本（PURG）在 MZ 双胞胎和 DZ 双胞胎之间有显著的表达差异；但在 FTC 中没有重复。通路分析强调了以前与 MZ 双胞胎相关的 WNT 通路，以及以前与 DZ 双胞胎相关的 TGF-B 和 SMAD 通路。对来自 NTR、FTC 和 FinnTwin12 的 2797 对 MZ 双胞胎和 2040 对 DZ 双胞胎的 169 种血清代谢物进行的元分析表明，代谢组没有差异。总之，我们没有发现 MZ 双胞胎和 DZ 双胞胎血液中可复制的转录水平表达差异，但强调了 TGF-B/SMAD 通路是 DZ 双胞胎的潜在转录生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

American Journal of Medical Genetics Part A 生物-遗传学

CiteScore

3.50

自引率

5.00%

发文量

432

审稿时长

2-4 weeks

期刊介绍： The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts: Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders. Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .