The Finnish genetic heritage in 2022-from diagnosis to translational research

Isolated populations have been valuable for the discovery of rare monogenic diseases and their causative genetic variants. Finnish disease heritage (FDH) is an example of a group of hereditary monogenic disorders caused by single major, usually autosomalrecessive, variants enriched in the population due to several past genetic drift events. Interestingly, distinct subpopulations have remained in Finland and have maintained their unique genetic repertoire. Thus, FDH diseases have persisted, facilitating vigorous research on the underlying molecular mechanisms and development of treatment options. This Review summarizes the current status of FDH, including the most recently discovered FDH disorders, and introduces a set of other recently identified diseases that share common features with the traditional FDH diseases. The Review also discusses a new era for population-based studies, which combine various forms of big data to identify novel genotype-phenotype associations behind more complex conditions, as exemplified here by the FinnGen project. In addition to the pathogenic variants with an unequivocal causative role in the disease phenotype, several risk alleles that correlate with certain phenotypic features have been identified among the Finns, further emphasizing the broad value of studying genetically isolated populations.

Automated summary

Isolated populations provide valuable resources for the study of rare monogenic diseases and their genetic variants. Finnish disease heritage (FDH) is an example of a group of hereditary monogenic disorders caused by enriched single major variants in the population due to past genetic drift events. This Review summarizes the current status of FDH, including recently discovered disorders and other related diseases, and discusses the use of population-based studies and big data for identifying new genotype-phenotype associations.