Extensive analysis provides new insights into carrier risks for rare diseases
Keywords:A study conducted by HUS and the University of Helsinki revealed that couples with Finnish genetic ancestry have approximately a 3% risk of being carriers of recessively inherited and X-chromosomal rare diseases.
Kaisa Kettunen, Ronja Hotakainen, Anna-Kaisa Anttonen ja Eveliina Salminen.
The study utilized the latest version of the gnomAD v4 genetic population database, which includes a total of 800,000 individuals, about 30,000 of whom are Finnish.
Researchers identified a total of 104 genes with a gene-specific cumulative carrier frequency of over 0.5% in the Finnish genetic ancestry group.
"The results of the study indicate a significant risk of being a carrier couple for a recessively inherited disease or an X-chromosomally inherited disease in virtually all population groups," says bioinformatician and doctoral student Ronja Hotakainen.
Rare diseases are often chronic and difficult to treat
The unique recessively inherited disease heritage of the Finnish population is caused by genetic bottlenecks and founder effects due to the population history. As a result, some diseases that are very rare elsewhere are more common in Finland, while others are significantly rarer.
Hereditary rare diseases cause about 10% of early childhood deaths. Rare diseases are often chronic, difficult to treat, and place a significant burden on patients, their families, and healthcare due to the extensive need for care. Effective medications for rare diseases are rarely available.
In recessive inheritance, both parents are healthy but carry the disease-causing variant in the same gene. In such cases, there is a 25% risk in each pregnancy that the child will be affected.
Carrier screening would offer opportunities but wouldn’t identify all diseases
The American College of Medical Genetics and Genomics (ACMG) recommends carrier screening for severe diseases with a carrier frequency of over 0.5%.
Currently, predictive genetic screening for couples is not offered in Finland.
"Of the identified genes, only 26 were known to be part of the Finnish disease heritage. Therefore, carrier screening for genes solely within the Finnish disease heritage would not detect a significant portion of serious early childhood diseases," says clinical geneticist and docent Eveliina Salminen.
The risk of all hereditary diseases could not be identified in advance with potential carrier screening, as some diseases are caused by new (de novo) genetic variants.
"On the other hand, the results now allow for the assessment and consideration whether carrier couples could be identified in advance in Finland as well. Identifying at-risk carrier couples in advance would offer them the opportunity to utilize, for example, preimplantation or prenatal genetic testing if they so wish".
Research article: Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries
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