The long lasting geographical and linguistic isolation, internal migrations, famines and rapid, recent expansions have moulded the population structure of Finland for thousands of years. Such population isolates provide exceptional opportunities for identification of genome variations underlying disease traits. When the unique population structure is combined with the one payer health care system, the harmonized training of physicians and tradition in epidemiological research Finland has become one the most interesting places for genetic epidemiology. The availability of large sample collections has stimulated large international collaborative projects such as the FinnGen and SISu (Sequencing Initiative Suomi) projects.
Diseases of specific interest in the Palotie group have been migraine, schizophrenia, epilepsy and some cardiovascular traits. The wealth of multiple large study samples enables the group to use different study designs for genome variant identification and verification and for the estimation of the size of the effect contributed by the variants. These include large collaborative genome wide association (GWAs) and sequencing studies and studies that utilize family structures and extreme population bottlenecks to identify low frequency variant detection.
FinnGen study launched in Finland in the autumn of 2017 is a unique study that combines genome information with digital health care data. The FinnGen study is an unprecedented global research project representing one of the largest studies of this type. Project aims to improve human health through genetic research, and ultimately identify new therapeutic targets and diagnostics for treating numerous diseases. The collaborative nature of the project is exceptional compare to many ongoing studies, and all the partners are working closely together to ensure appropriate transparency, data security and ownership.
FinnGen brings together Finnish universities, wellbeing services counties, THL, Finnish Red Cross Blood Service, biobanks, international pharmaceutical companies and 520 000 Finns. Collaboration is the key to achieving breakthroughs in disease prevention, diagnosis, and treatment.
The group has over 20 years track record in migraine genetics. It builds on a long collaboration between Dr. Mikko Kallela and Dr. Maija Wessman and the very large collection of Finnish migraine families, consisting of more than 1 700 families with DNA from about 10 000 family members. Dr. Palotie has chaired the International Headache Genetics Consortium (IHGC) consisting of more than 30 groups around the world. IHGC is performing large genome wide association studies (GWAS) and has identified numerous genome loci associated to migraine. Current projects include expanded GWA studies led by Professor Matti Pirinen's group to uncover more of the genomic landscape underlying migraine susceptibility.
Most of the current population in the north-eastern part of Finland are descendants of small founder populations established in the 17th century. This has resulted in population isolate structures in the region and an enrichment of recessive diseases. These areas also have higher prevalence of schizophrenia and government compensation for cognitive disability. We therefore initially hypothesized that some recessive-acting variants enriched in this area might contribute to some forms of cognitive impairment. This hypothesis was demonstrated in case of a homozygote variant resulting in the CRADD disease. However, most of the genetic background identified in this cohort is explained by other than strong acting recessive variants. Furthermore, while the contribution of de novo variants in more severe forms of intellectual disability (ID) has been extensively studied, less is known about genetic architecture of mild ID.
In collaboration with Dr. Outi Kuismin (FIMM, University of Oulu, Oulu University Hospital), Olli Pietiläinen (University of Helsinki, Neuroscience Center, HiLIFE) and Dr. Jukka Moilanen (University of Oulu, Oulu University Hospital) we collected a comprehensive sample of patients with an unknown cognitive impairment etiology residing in Northern Finland. The cohort represents an unselected population of ID patients, and therefore most of the patients have the most common, mild form of ID. The NFID collection consists of 1562 cases and additional 2500 family members.
Using exome sequencing and DNA microarray genotyping we showed that rare damaging variants in known ID genes are observed significantly more often in severe than in mild ID patients. We also showed that a common variant polygenic risk significantly contributes to ID. Additionally, we identified a Finnish enriched homozygous variant in the CRADD ID-associated gene (Kurki et al. 2019, Urpa et al 2023).
We are currently extending the NFID collection and as of January 2020 have collected approximately 3000 cases (~1400 cases and ~1600 family members) in approximately 1250 families. Currently we are particularly focusing on inherited variants in large multiplex families (families with three or more individuals with ID).
The Finnish SUPER study on genetic mechanisms of psychotic disorders is a part of the international Stanley Global Neuropsychiatric Genomics Initiative. The objective of the study is to better understand the genetic and biological background of psychotic disorders in order to provide more accurate information for the development of new therapeutic interventions. In Finland the national study and participant recruitment was carried out during the years 2016-2018. The Finnish SUPER study successfully collected over 10,400 genetic samples from psychosis patients. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, was leading the study in collaboration with the National Institute for Health and Welfare (THL). Five university hospital districts were involved in the sample collection. All samples have been GWAS genotyped and exome or whole genome sequenced. The access to data from national health registers enables longitudinal analyses of disease trajectories over individual’s lifespan. This has enabled us to investigate the genetic contribution of different disease outcomes (Kämpe et al 2023). This data also contributes to the SCHEMA consortium that aims to identify very rare, high risk coding variants that could shed light to biological processes that contribute to psychosis susceptibility.