MedCity Influencers, Diagnostics

Accumulated genetic variations: What they are and why they matter to a complete health picture 

Unlike inherited genetic predispositions, accumulated genetic changes are the result of environmental influences, such as smoking, chemicals or ultra-violet radiation. A growing body of research links somatic changes to an increased likelihood of blood cancers and cardiovascular disease, both heart disease and stroke.

 

Genes are by no means a crystal ball, but they can be used to forecast susceptibility to a variety of conditions, from cancers and heart disease to chronic inflammatory conditions. As such, they can help healthcare professionals and patients make better care decisions.

Generally speaking, when people today think about genetic predispositions, they think about their parents and family trees. However, those inherited genetic variations bequeathed by our parents and grandparents are only a portion of a complete genetic picture – and often not the most revealing one. The genetic variations most commonly linked to disease are actually?not?the ones from your parents; rather, they are acquired as one ages.

Mom and Dad Can’t Take All the Heat for All Health Challenges
Unlike inherited genetic predispositions, accumulated genetic changes (otherwise known as “somatic”) are the result of environmental influences, such as smoking, chemicals or ultra-violet radiation. They can also stem from common errors cells make as they duplicate themselves over time. The expansion of these detrimental variations cause damage to DNA within blood cells, a phenomenon known as clonal hematopoiesis (CH), which increases susceptibility to many diseases, including many types of cancer.

Germline variations in genes still indicate potential vulnerabilities, with one in five healthy adults estimated to carry an inherited marker. However, these genetic abnormalities represent a static metric. Once individuals are tested for inherited variations, they will never need to do so again. What’s more, many of the predispositions that surfaced through this testing can be addressed through lifestyle and medical interventions. It boils down to being aware of them.

Somatic changes, on the other hand, can happen at any stage of life. While many of these changes have no clinical ramifications, some of them can exacerbate predispositions inherited from our parents because the disease is often the result of multiple genetic variations banding together, inherited or acquired.

The chances of an acquired variation accumulating and accelerating within the body increase significantly as we age, generally after the age of 40 and growing each decade. This could drastically change a patient’s health profile, casting inherited vulnerabilities into a new light without any warning or symptoms.

Understanding Accumulated Variations
A growing body of research links somatic changes to an increased likelihood of blood cancers and cardiovascular disease, both heart disease and stroke. The same research reveals that these accumulated genetic variations contribute to infection and severe inflammatory reactions, some of which are associated with severe cases of Covid-19.

A study conducted by JAMA Cardiology explores the connection between accumulated genetic change and a pro-inflammatory immune response that resembles the exaggerated cytokine release syndrome (CRS) experienced by patients with severe Covid-19. Notably, the research found that patients who experienced the most extreme inflammatory response carried variations TET2 and DMNT3A, both of which accumulate in genes over time.

Another research report published in Cancers analyzing patients hospitalized with severe Covid-19 disease found a much higher frequency of clonal hematopoiesis (CH) of indeterminate potential (sometimes called clonal hematopoiesis of indeterminate potential or CHIP) ), an age-associated condition in cells, in all age groups.

Additionally, accumulated DNA damage to the JAK2 gene has been found in a large proportion of cancer-free patients with venous thrombosis, a known complication of Covid-19. While preliminary, the findings demonstrate compelling correlations between somatic genetic change and Covid-19 severity that could be used to identify patients prone to complications early, intervene sooner and inform treatment strategies.

It is believed that providers can apply these correlations to other areas of care to assess an individual’s susceptibility to a wide range of diseases, and ultimately improve and extend quality of life.

Improving Care Decisions with Somatic insights   
Augmenting current health assessments and care strategies with accumulated genetic data can open new pathways for disease detection, response and prevention. The scientific and medical communities have only scratched the surface of what we can learn from these insights. Even so, understanding somatic damage shows great promise for helping individuals stay ahead of their health concerns and respond in a more informed way.

Photo: Andy, Getty Images


Avatar photo
Avatar photo

Dr. Salvatore Viscomi

Dr. Viscomi is the chief medical officer of GoodCell and a practicing physician, researcher, instructor and entrepreneur. He spent 14 years as a member of Harvard Medical Schools teaching faculty. Recognized as an expert in his field, Salvatore has published and presented nationally and internationally. While on clinical staff at Brigham and Women’s Hospital, he co-founded Brigham NightWatch, one of the ?rst teleradiology networks in the world.

He also served as an executive and board member of FreMon Scienti?c Inc. where he led the development of a next-generation blood product management solution through FDA approval and to market. He now chairs their Professional Advisory Board.

Dr. Viscomi began his path towards medicine while at Columbia University, earning a B.A. in Neuropsychology. Salvatore completed his residency and specialization at Harvard Medical School. He also serves on the mission delivery committee of Make-A-Wish Foundation. In 2016, Dr. Viscomi completed the Executive Education Program at Harvard Business School.

This post appears through the MedCity Influencers program. Anyone can publish their perspective on business and innovation in healthcare on MedCity News through MedCity Influencers. Click here to find out how.

Shares0
Shares0