Approved research

Dissemination of shared genetics across phenotypes associated with reproductive health and related endophenotypes

Lay summary

International consortia efforts have made it possible to collect large numbers of samples for many common diseases and have successfully revealed thousands of disease-related genetic loci. Recently developed methods make it possible to compare the shared genetic components of phenotypes, based on their genome-wide association study (GWAS) summary statistics, allowing us to detect genetic pathways underlying reproductive health-related traits and disorders and to compare them to a broad selection of endophenotypes (hormone levels, metabolites, glycaemic traits etc.) We plan to use both single variant genotype data as well as copy number variant (CNV) data, which we will obtain from the raw genotype intensities. The proposed research is in the public interest as the possible determination of genetic variants and genetic pathways underlying reproductive health-related traits and disorders can provide us with useful etiological insights into these traits and can hopefully help us to discover novel causal genetic mechanisms and potential biomarkers. Within this project we plan to run GWAS analyses using single marker, CNV and gene-wise burden tests, and combine the results with available data on traits from other cohorts in meta-analysis. As the next step we will run LD score regression across all phenotype pairs to discover their shared genetic components. Bi-directional Mendelian randomisation will then used to discover possible causal effects. The international research team consists of specialists from various scientific fields, including reproductive medicine, statistics, genomics and genetic epidemiology, thereby creating a favorable synergy for interdisciplinary high-quality research. The research will use the entire UK Biobank cohort with available genotype data.