A new study shows that 4% of Icelanders carry a genotype associated with severe disease that affects their lifespan. The study, which analyzed 58,000 Icelanders whose whole genomes were sequenced, found that actionable genotypes, particularly those predisposing to cancer and cardiovascular disease, significantly shorten life expectancy. The findings led to a national precision medicine initiative in Iceland, highlighting the potential of genomic data to improve healthcare and patient outcomes.
Scientists at deCODEgenetics, a subsidiary of Amgen, published a study exploring the relationship between specific genotypes found in the Icelandic population and their impact on lifespan. This research prompted the Icelandic government to launch a comprehensive precision medicine program. Precision medicine relies heavily on large amounts of data in genomics, transcriptomics, and proteomics, and Icelanders are uniquely positioned in these areas because they have unprecedented access to this data.
The study, published recently in the New England Journal of Medicine, focused on genotypes that increase disease risk and for which preventive or therapeutic measures are already in place. These genotypes are called actionable genotypes. The scientists used a population-based dataset of 58,000 Icelanders whose whole genomes were sequenced to assess the proportion of individuals carrying actionable genotypes.
Using a list of 73 testable genes from the American College of Medical Genetics and Genomics (ACMG) guidelines, the scientists found that 4% of Icelanders carry a testable genotype of one or more of these genes. Diseases caused by these genotypes include cardiovascular disease, cancer, and metabolic disease.
Actionable genotype effects on lifespan
This study evaluated the relationship between actionable genotypes and the longevity of their carriers. The largest effects were observed among carriers of cancer-prone genotypes, whose median survival was three years shorter than noncarriers. BRCA2 pathogenic variants that predispose to breast, ovarian and pancreatic cancer shorten life span by seven years, and LDLR variants that cause high cholesterol and cardiovascular disease shorten life by six years. "Our results show that the actionable genotypes identified in our study all contribute to severe disease, and they may have a dramatic impact on lifespan," said paper author Patrick Sulem, a scientist at deCODE Genetics.
The results suggest that carriers of specific actionable genotypes are more likely to die from diseases caused by those genotypes. Carriers of BRCA2 pathogenic variants are seven times more likely to die from breast, ovarian or pancreatic cancer.
In addition, they were 3.5 times more likely to develop prostate cancer and seven times more likely to die from prostate cancer than people who did not carry the variant.
The researchers found that 1 in 25 people carried the actionable genotype and had a shorter life expectancy on average. Identifying and disclosing actionable genotypes to participants can guide clinical decisions, thereby improving patient outcomes. "This knowledge therefore has great potential to reduce the burden of disease on individuals and society as a whole," said Kari Stefansson, author of the paper and CEO of deCODEgenetics.
Compiled from /scitechdaily