Unzipping the Links Between Genetics and Disease

While treating patients with Hyperimmunoglobulin E syndrome (hyper IgE syndrome), a condition caused by a genetic mutation that weakens the immune system. Dr. Alexandra Freeman noticed an interesting link to the symptoms of Covid-19. Freeman, who is a senior clinician in the National Institute of Allergy and Infectious Diseases, expected that Covid-19 would be more likely to adversely affect people with the syndrome than people who were not immune compromised. Instead she found that the “majority of the patients with hyper IgE syndrome, when they’ve had Covid-19, have done just fine.” What is happening at the genetic level for such an outcome to occur? 

Genetics influences every aspect of an individual’s life–their diet, the way they act, and how they respond to stimuli. In response to the multitude of diseases that have taken the world by storm in the past decade, host genetics is becoming an increasingly relevant topic. 

Host genetics revolves around the idea that an individual’s genetic makeup can significantly alter their susceptibility to infectious disease. Whether it be minor gene mutations or a more serious disorder, genetics accounts for much of the variability in disease susceptibility among individuals. Host genetics delves deeper into the now well-accepted germ theory, which states that pathogens spread disease. Germ theory, however,  does not factor in unique hereditary quirks. To dive into this idea of host genetics, scientists in Denmark ran a study on 960 adopted children. They wanted to evaluate the children’s risks of passing away from an infectious disease if their biological parents did so before the age of 50. The goal of the study was to find a biological link that would suggest a similarity in infectious-disease susceptibility, and it did just that. The study showed that the adopted children had a  5.81% greater risk of succumbing to the same infectious disease as their biological parent. While this number may seem low, it was a revelation for scientists at the time: They had proved the importance of host genetics when considering infectious disease outcomes and how they may affect individuals. 

Freeman’s research on hyper IgE syndrome – an immunodeficiency primarily caused by a genetic mutation of the STAT3 gene – studied this phenomenon even further. In her trials and daily interaction with patients, she noticed something interesting in those with the syndrome. When immunocompetent people, or those with healthy immune systems, contract Covid-19, the immune response to fighting off the virus is what causes a majority of the negative symptoms even weeks later. Serious symptoms are treated with medications to suppress the immune system in its severe ways of attacking the virus. However, for people with hyper IgE syndrome, “they already kind of have, built into their bodies, some of these medicines that were being used,” Freeman said. This basically meant that those patients did not need any medicinal intervention if their symptoms were related to the immune-system response, so they did not feel as sick in general. 

The genetic mutation that causes hyper IgE syndrome is genetically dominant, meaning there is a higher likelihood that it can be passed down through generations if it is present in either parent. While the negatives of the syndrome do outweigh positives like this disease response, it reveals that such situations are possible and can be due to genetic differences. In a similar way, a genetic trend can be noticed directly to Covid-19.Some individuals possess a gene that causes T cells in their immune system  to detect SARS-Cov-2, the virus that causes Covid-19, and similar seasonal coronavirus strains.These individuals have a lesser chance of having a serious negative reaction if they contract the virus because their immune system can detect and fight off invaders quicker. Using this knowledge, genetics-related testing can change the world of disease control. 

According to Freeman, advancements in individualized genetic testing can significantly enhance the control of infectious-disease outbreaks. By enabling public health officials to better identify and manage populations based on their genetic susceptibility – for example, through quarantines and personalized therapy plans – there is a better chance at keeping the rapid spread of disease at bay. Moreover, introducing research scientists and doctors to the many genetic factors that play into infectious-disease susceptibility can greatly affect the world of modern medicine and may lead to the creation of more effective antibiotics and antivirals that are more specifically targeted to groups based on how their body will respond. She added that while there may still be a long way to go in fully understanding the intersection of genetics with other factors, scientists are unlocking more and more each day to grasp the role it plays in our lives.