Beyond chromosomal abnormalities: deciphering the genetic drivers of miscarriage

The ultimate goal of this project is to identify the fetal genetic effects on miscarriage beyond chromosomal abnormalities and understand its phenotypic consequences in pre-implantation embryos and live-born individuals.

We will address the following unanswered questions:What is the role of the fetal genome in miscarriage etiology beyond chromosomal abnormalities?Can we decompose the heterogeneity of miscarriage into biologically meaningful sub-phenotypes?What are the consequences of a high genetic risk to miscarriage in pre-implantation embryos and live-born individuals?I will exploit the correlation between the genome of the miscarried fetus and that of its “siblings” to perform a genome-wide association studies in >500,000 samples.

The unique potential of this proposal derives from a shift in the perspective on the etiology of miscarriage, challenging the long-held view that the fetal genetic effects on miscarriages are limited to chromosomal abnormalities.

I will develop novel computational tools to integrate large-scale genomic data, regulatory effects from individual cells, open-access genotyping arrays of embryos and register data from Nordic countries.

When this project is completed, we should have information on miscarriage sub-phenotypes, gene targets for miscarriage prevention and diagnostic work-up, the consequences of miscarriage risk in live-born individuals and new methods and tools to push scientific boundaries in reproductive genetics.