Approximately 4% of individuals bear a genetic makeup linked to potential lifespan reduction.
In a groundbreaking study published in the New England Journal of Medicine, scientists at deCODE genetics—a subsidiary of Amgen—have identified common actionable genotypes in the Icelandic population that are linked to reduced lifespan. The findings have sparked interest from the Icelandic government, prompting them to announce a nationwide effort in precision medicine.
The research focuses on genotypes that heighten the risk of developing a disease for which preventive or therapeutic measures are available, known as actionable genotypes. The scientists utilized a population-based data set consisting of more than 58,000 whole-genome sequenced Icelanders to measure the percentage of individuals carrying these actionable genotypes.
Using a list of 73 actionable genes from the guidelines provided by the American College of Medical Genetics and Genomics (ACMG), the study found that 4% of Icelanders carry an actionable genotype in one or more of these genes. These genotypes contribute to cardiovascular, cancer, and metabolic diseases.
The researchers examined the correlation between actionable genotypes and the lifespan of their carriers. Carriers of cancer-predisposing genotypes were found to have a median survival three years shorter than non-carriers. Genotypes such as a pathogenic variant in BRCA2, which increases the risk of breast, ovarian, and pancreatic cancer, decreased lifespan by seven years. Another variant in LDLR, linked to high cholesterol levels and cardiovascular disease, reduced lifespan by six years.
Patrick Sulem, an author on the paper and scientist at deCODE genetics, stated, "Our findings suggest that the actionable genotypes identified in our study, all predicted to cause serious disease, could have a drastic impact on lifespan."
The results also indicated that those who carried specific actionable genotypes were more likely to have died from the diseases associated with those genotypes. For example, individuals harboring a pathogenic variant in BRCA2 have a seven-fold risk of succumbing to breast, ovarian, or pancreatic cancer. They are also 3.5 times more likely to develop prostate cancer and seven times more likely to perish from prostate cancer compared to those who do not carry the variant.
Recent research highlights the Icelandic population’s notability for a protective mutation in the amyloid precursor protein gene (AβPP), which shields carriers from Alzheimer’s disease and related cognitive decline. This mutation demonstrates how certain genotypes can have an "actionable" impact, affecting neurodegenerative disease risk and lifespan outcomes in Icelanders.
Kari Stefansson, another author of the paper and CEO of deCODE genetics, commented, "The identification and disclosure of actionable genotypes to participants can guide clinical decision-making, potentially leading to improved patient outcomes. This knowledge has significant potential to alleviate disease burden for individuals and society as a whole."
The study concluded that 1 in 25 individuals carried an actionable genotype and, on average, have a reduced lifespan. The results underscore the importance of precision medicine initiatives in the Icelandic population.
- The research in precision medicine, spearheaded by the Icelandic government, focuses on actionable genotypes linked to medical-conditions such as cardiovascular diseases, cancer, and metabolic diseases, derived from a study published in the New England Journal of Medicine.
- The groundbreaking study identified that 4% of Icelanders carry an actionable genotype in one or more of the 73 actionable genes, which is significant because these genotypes contribute to health-and-wellness issues like cardiovascular, cancer, and mental health.
- In the study, carriers of cancer-predisposing genotypes were found to have a reduced lifespan, with carriers of a pathogenic variant in BRCA2 losing seven years and those with a variant in LDLR losing six years.
- With the identification of actionable genotypes, Kari Stefansson, another author of the paper and CEO of deCODE genetics, highlights the potential for improved patient outcomes by guiding clinical decision-making and alleviating disease burden for individuals and society as a whole.
