M2 internship: Characterisation of pleiotropy of non-coding regulatory variants

 Stage · Stage M2  · 6 mois    Bac+5 / Master   TAGC/INSERM U1090 · Marseille (France)

 Date de prise de poste : 2 janvier 2023


pleiotropy human diseases genetic variants gene regulation bioinformatics genetics genomics cis-regulatory elements epigenetics


Genome-wide association studies (GWAS) have shown that pleiotropic genetic variants affecting multiple traits are relatively common in the genome. A large majority of these variants fall in non-coding regions and are likely gene regulatory variants. The molecular basis of the genetic pleiotropy is not well understood. For instance, do pleiotropic regulatory variants affect more genes than usual? Or do downstream genes of pleiotropic variants more pleiotropic than in average? To answer these questions, we will use our recently developed eQTL/GWAS co-localization pipeline to select highly pleiotropic genetic regulatory variants and investigate their effect on downstream genes and traits.

In this internship, we would like to compute causality between regulatory variants and downstream genes to evaluate different hypothesis regarding pleiotropy of regulatory variants. To compute causality, we plan to use Mendelian randomization and mediate analysis between regulatory variants and downstream genes in co-localized eQTLs and GWAS variants. These analyses might allow to better understand the mechanism of genetic pleiotropy in the human genome.


- A global overview of pleiotropy and genetic architecture in complex traits. 2019. DOI:10.1038/s41588-019-0481-0
- Trait-Associated SNPs Are More Likely to Be eQTLs: Annotation to Enhance Discovery from GWAS. 2010. DOI:10.1371/journal.pgen.1000888
- The impact of cell type and context-dependent regulatory variants on human immune traits. 2021. DOI:10.1186/s13059-021-02334-x



Procédure : Envoyer un email à: aitor.gonzalez@univ-amu.fr

Date limite : 1 mars 2023


Aitor González


Offre publiée le 2 août 2022, affichage jusqu'au 1 mars 2023