The interaction between genetics and the impact of the COVID-19 pandemic on individuals’ wellbeing over time

By Dr. Liji Thomas, MDMay 23 2022Reviewed by Danielle Ellis, B.Sc.

While the coronavirus disease 2019 (COVID-19) pandemic affected the whole world in many ways, hitting community-based social interactions, economic activity, and health status simultaneously, the impact produced different levels of distress in different individuals. Some, for instance, drifted far into depression, while others showed a high degree of resilience.

A new paper looks at the genetic contribution to individual wellbeing during the pandemic, seeking to find support for the hypothesis that this is an important factor interacting with the pandemic, a potentially traumatic event, and thus helping to shape the outcome.

What did the study show?

The study, which appears in PLOS Genetics, examined how genetics affected the physical and mental health and behavioral patterns related to lifestyle, using data from the Lifelines biobank. This is a prospective cohort study involving 167,000 participants from three Dutch provinces.

The study involved following up with over 17,800 individuals over time concerning their physical health, mental health, and lifestyle behaviors and comparing these results with their genotype data. The current paper reports the findings from the 19 survey forms sent out over the ten months at the beginning of the survey.

The researchers looked at the risk of various outcomes, including the body mass index (BMI), susceptibility to and severity of COVID-19, educational levels, personality, and behavioral traits, psychiatric illness, and life satisfaction. They also looked at heritability estimates and the proportion to which the environmental component could explain the variability in the scores. Based on genome-wide association studies (GWASs), they calculated polygenic scores (PGS) for these outcomes.

At baseline, they found that high PGS for psychiatric illness was linked to a higher likelihood of tiredness, exhaustion, health symptoms, and personality traits like nervousness. Conversely, high PGS for life satisfaction correlated with lower physical complaints. Therefore, people with high scores for psychological traits had lower scores for wellbeing and related parameters.

Interestingly, several PGS were also associated with the outcomes of COVID-19-related questions like trust in the government’s response to the pandemic, implementing non-pharmaceutical interventions, and worry outcomes. The PGS for drinking was related to whether individuals avoided bars and restaurants during COVID-19 as a precaution to limit transmission.

The researchers also compared the PGS-question pairs at baseline and at later time points. This showed a change over time for 11 of them, with two being true positives: COVID-19 susceptibility was correlated with a positive test for the virus, and life satisfaction with feeling tired.

Over time, there was a decline in wellbeing related to PGS for life satisfaction, neuroticism, and depression. The perceived quality of life peaked during the summer of 2020, beginning to fall after that. However, this was positively affected by the PGS for life satisfaction.

Those with higher life satisfaction PGS were more resilient, while a lower PGS predicted a lower final perceived quality of life. This shows the increasing role of genetic predisposition across the pandemic.

Reasons for increasing genetic contributions

Some explanations may be offered for this phenomenon. For one, the limited social interactions could negatively affect wellbeing, which then became more dependent on the genetic contribution. A second reason could be that people genetically predisposed to depression become depressed when exposed to trauma. At the same time, neurotic predisposition results in a more extreme response when faced with stress-inducing situations.

This could explain why people felt less resilient at a later timepoint, as they had faced more stress over this period, as well as why those with lower life satisfaction struggled more during the pandemic.

A third explanation is that the strong disruptive effect of the pandemic and the lockdown reduced the quality of life so much that the genetic effect sank into relative insignificance. As the pandemic progressed, the accompanying stress waned, increasing the relative but not the absolute contribution of the genetic element. This is supported by findings from the Twins Early Development Study, where well-being outcomes were comparable in heritability irrespective of the origin of the pandemic.  

Genetic basis for COVID-19 infection risk

The number of infections increased rapidly over time, and there was a correlation between the PGS for susceptibility and infection risk. However, the genetic contribution waned over time. This effect may have been due to the greater proportion of hospitalized patients among the susceptibility cohort, which skewed the signal towards disease severity and not infection per se.

Another possibility is that the change in dominant variants from D614G to Alpha, which occurred towards the end of the study, increased the infectivity of the circulating variant, making the genetic component less significant.

What are the implications?

The findings of this study show a small but increasing genetic contribution to wellbeing over time. This could change as PGS becomes more accurate since larger effect sizes are expected, based on the study of other conditions. Secondly, it is clear that the duration of a stressful environmental event also modulates the contribution of the genetic predisposition to the eventual outcome.

This brings the importance of longitudinal data into prominence. This can be analyzed using GWAS techniques to better detect and predict the risk categories of patients with these variables.

We have been in the unique position to observe a synchronized and prolonged exposure to a shared continuous stress factor and an increasingly abundant infectious disease. Our results indicate that participant’s responses to the COVID-19 pandemic were at least partially driven by their genetic predisposition and that this genetic contribution changes over time.”