Abstract
AbstractMonozygotic (MZ) and dizygotic (DZ) twins are often studied to determine genetic and environmental influences on complex traits, however, the biological mechanisms behind MZ and DZ twinning are not completely understood. Genomic and epigenomic studies have identified SNPs associated with DZ twinning and DNA methylation sites associated with MZ twinning. To enhance the discovery of molecular biomarkers of twinning, we compare transcriptomics and metabolomics data from MZ with those from DZ twins. We compared 42,663 RNA transcripts in 1,453 MZ twins and 1,294 DZ twins from the Netherlands Twin Register (NTR), followed by sex-stratified analyses. The 5% transcripts with lowest p-values were selected for replication analysis in 217 MZ and 158 DZ twins from the older Finnish Twin cohort (FTC). In the NTR sample, we observed upregulations of the protein codingPURGgene in MZ twins. The female-only analyses confirmed thePURGgene and identified four other genes, while the male-only analyses indicated three other genes associated with either MZ and DZ twinning. Replication results in the FTC, did not confirmPURG, but revealed seven differentially expressed genes with nominal significant p-values in both cohorts, none of which have been implicated for twinning before. Pathway enrichment showed differences in expression in the WNT-pathway and cell adhesion processes, which were previously indicated with MZ twinning though an epigenetic study, and the TGF-B pathway known to be associated with DZ twinning through genetic studies. We additionally meta-analyzed 169 serum metabolites from a NMR platform in 2,797 MZ and 2,040 DZ twins from the NTR, FTC and the FinnTwin12 (FT12), and show no metabolomic differences between the MZ and DZ twins. Overall, we identified novel transcriptomics biomarkers of twinning in peripheral blood and provide partial converging evidence for multiple pathways previously identified in the GWAS of DZ and EWAS of MZ twinning.
Publisher
Cold Spring Harbor Laboratory