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Master of Science in Omics Data Analysis | Universitat de Vic - Universitat Central de Catalunya
Final Master Project | Antonio Gómez-Martín | 19th September 2023
Supervisor: Mariona Bustamante | Co-supervisor: Dolors Pelegrí-Sisó
Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
The placenta, of foetal origin but situated at the interface between mother and foetus, plays a central role in foetal growth and development. Placental function is influenced by both the foetal and maternal genomes, with effects mediated through direct and indirect mechanisms that involve complex interactions between various foetal and maternal cell types. Dysregulation of placental microRNAs (miRNAs), which are small non-coding RNAs that control gene expression post-transcriptionally, has been associated with various pregnancy-related complications and adverse birth outcomes. The aim of this study was to identify maternal trans-subject miRNA-expression quantitative trait loci (i.e. miR-eQTLs, maternal genetic variants associated with the expression of placental miRNAs through trans subject effects). In particular, we investigated the association of genome-wide maternal single-nucleotide polymorphisms (SNPs) with the expression of 388 miRNAs in the placentas of 271 mother-child pairs from a subset of European mothers of the population-based Barcelona Life Study Cohort (BiSC). Genotyping was done using a SNP array platform, and placental miRNA levels were measured through next-generation sequencing. The association between SNPs and miRNA was tested using linear regression models adjusted for confounders using the TensorQTL tool. After multiple testing correction, we found 11 miR-eQTLs representing 10 loci and 12 miRNAs showing both positive and inverse associations. Two of these miR-eQTLs are potentially caused by cis effects of the foetal genome as the SNP-miRNA pairs were found to be closely located in the genome. The other nine are considered potentially caused by trans effects of the maternal genome, marking the first identification of maternal trans-subject miR-eQTLs associated with placental expression of miRNAs. Some maternal miR-eQTLs pointed to genes related to inflammation and hormone regulation, key processes for the progression of pregnancy. Moreover, associated miRNAs had previously been associated with pregnancy complications such as preeclampsia or gestational diabetes. Results from this study provide knowledge about the maternal trans-subject genetic effects to the functioning of the placenta. This information can be used in future studies to develop diagnostic tools, and treatments to prevent pregnancy complications.
- TFM_AGomez_00_ServerCommands.sh
- TFM_AGomez_01_GWAS_1_prepareDB.R
- TFM_AGomez_02_GWAS_2_QC.sh
- TFM_AGomez_03_GWAS_3_Imputation.sh
- TFM_AGomez_04_GWAS_4_run_imputation.sh
- TFM_AGomez_05_miQTL_1_prepareDB.R
- TFM_AGomez_06_miQTL_2_TendorQTL_trans.py
- TFM_AGomez_07_miQTL_3_merge_miRNA.R
- TFM_AGomez_08_FUMA_prepareDB.R
- TFM_AGomez_09_Graphics.R
- TFM_AGomez_10_Tables.R