NEW YORK – Researchers involved with Finland's FinnGen study reported discoveries in Nature on Wednesday that they say demonstrate the utility of studying isolated populations such as the Finnish to discover low-frequency, high-impact variants for common diseases.
Investigators from the University of Helsinki and the Broad Institute led the study, which looked at the effects of 44,370 variants on more than 1,900 diseases in participants in Finnish biobanks for whom genotype and phenotypic data was available. According to the paper, they were able to identify almost 2,500 genomic regions linked to the diseases surveyed.
Among these, fine-mapping turned up 148 coding variants that were associated with 83 endpoints linked in other studies to conditions such as retinal dystrophy, hearing loss, and female infertility. Ninety-one of them had an allele frequency of less than 5 percent in non-Finnish Europeans, of which 62 were found to be enriched more than twofold in Finns. As part of the study, the researchers also carried out a meta-analysis of biobank data from Estonia and the UK.
Mark Daly, director of the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki, said in a statement that the findings "demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through variants that are rather rare, but have a strong biological impact."
Since 2017, Finnish researchers and private-sector partners have been involved in genotyping and collecting data on participants in Finnish biobanks in a cohort that is expected to surpass 500,000 people this year. For the study published in Nature, they analyzed a cohort of 224,737 participants for whom data was available at the time. Most of the FinnGen participants have been genotyped using a custom Axiom microarray manufactured by Thermo Fisher Scientific.
Aarno Palotie, scientific director of FinnGen and a professor at FIMM, noted in a statement that even with data from less than half of the FinnGen cohort, the researchers were able to make a "wealth of important genetic discoveries," including novel risk and protective variants for both common and rare diseases.
According to the study's authors, the Finnish population is ideal for studying genetic diseases, particularly recessively inherited ones where both parents carry a rare causal variant. As noted in the paper, Finland, which has a population of 5.5 million people, experienced a population bottleneck about 120 generations ago, after which the population rapidly expanded. This means that rare, potentially causal variants are present at a higher frequency in the local population, while fewer rare variants are found in the Finnish population overall.