Having published the study in the New England Journal of Medicine today, scientists have identified genotypes that increase the risk of a specific disease for which preventive or therapeutic measures have been established. It was determined that these genotypes are actionable genotypes. In order to determine the fraction of Icelanders with actionable genotypes, the researchers used a population-based data set of 58,000 whole-genome sequenced Icelanders.
It has been found that 4% of Icelanders carry an actionable genotype in one or more of the genes listed in the guidelines of the American College of Medical Genetics and Genomics (ACMG), which are based on a list of 73 actionable genes. Several diseases are caused by these genotypes, including cardiovascular disease, cancer, and metabolic disease.
Using a list of 73 actionable genes from the guidelines of the American College of Medical Genetics and Genomics (ACMG), the scientists discovered that about 4% of Icelanders carry a genotype for one or more of these genes, which could result in actionable health effects. Among the diseases caused by these genotypes are cardiovascular disease, cancer, and metabolic diseases.
According to the study, the relationship between actionable genotypes and the lifespan of the carriers of these genotypes was assessed. In particular, the biggest effect was observed among those who carry cancer-predisposing genotypes, who had three years shorter median survival than those who did not carry these genes. A pathogenic variant in the gene BRCA2, predisposing to breast, ovarian, and pancreatic cancer, shortened life expectancy by seven years and a pathogenic variant in the gene LDLR, which causes high levels of cholesterol and cardiovascular disease, shortened life expectancy by six years. "We have shown that the actionable genotypes identified in our study, which are all predicted to cause serious disease, may have a profound effect on living a long and healthy life".According to Patrick Sulem, one of the authors on the paper and a scientist at deCODE genetics,
According to Patrick Sulem, one of the authors on the paper and a scientist at deCODE genetics,
According to the results of the study, individuals who carry particular actionable genotypes have a seven-fold increased risk of dying from cancers caused by these genotypes. For example, individuals with a pathogenic variant in BRCA2 have an eight-fold higher risk of dying from pancreatic, ovarian or breast cancer.
Furthermore, those who have the variant are 3.5 times more likely to develop prostate cancer and 7 times more likely to die from prostate cancer than those who do not carry the variant.
As the researchers determined, 1 in 25 people possessed an actionable genotype and, on average, had a shorter lifespan. As a result of the identification and disclosure of actionable genotypes among participants, clinical decision-making can be facilitated, which may lead to improved patient outcomes. Therefore, this knowledge has significant potential to reduce disease burden for individuals as well as society as a whole," says Kari Stefansson, co-author of the paper and CEO of deCODE genetics.

Source prnewswire