RepSIC · Repeat variants shaping disease risk in FinnGen and Estonian Biobank cohorts

A substantial proportion of the human genome consists of repetitive content, until recently discarded as “junk DNA”. These include tandem repeats (TRs)—stretches of short sequence motifs repeated consecutively—and mobile elements (MEs), or interspersed repeats capable of replicating and inserting themselves into new genomic locations. Despite their abundance and likely major contribution to disease, repeat variants have been largely neglected in genetic association studies, primarily due to the limited resolution of standard discovery and genotyping methods.The aim of my MSCA Postdoctoral Fellowship project is to systematically detect and characterise the effects of repeat variants on human traits and diseases. To make TRs and MEs accessible in large population biobanks with mainly microarray data available, I will develop an advanced haplotype-informed framework for repeat variant discovery and imputation, applying it to FinnGen and Estonian Biobank—two cohorts distinguished by exceptionally high population representation and dense familial relatedness in Europe. In the Estonian Biobank specifically, I will leverage long-read sequencing data to construct what will be, to my knowledge, the most comprehensive reference panel of repeat variants to date. The imputed variants will then undergo association testing with rich registry-linked phenotypic data.Given the overall scarcity of repeat-focused studies at biobank-scale, this project is well positioned to uncover a substantial number of previously unreported phenotype associations. By filling this gap, the project has the potential to deliver novel biological insights into how repeat variants influence human traits and diseases, leading to improved risk prediction and population health.