Genetics and age in COVID-19 susceptibility

Genetics and age in COVID-19 susceptibility

The questions below are based on the following article: Nakanishi T et al. Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality. 

Reference:

J Clin Invest. (2021); JCI – Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

All the information you need to answer the questions is listed below, you do not need to refer to the article.

Background: rs10490770 is a mutation on chromosome 3 to increase the risk of severe COVID-19 outcomes. In this problem set, carrier/noncarrier designations refer specifically to this mutation. Below are tables summarizing frequencies of COVID-related deaths or severe respiratory failure (let’s call these ‘adverse outcomes’). 

Calculate and interpret the odds ratio of adverse outcomes associated with being a carrier. Is it a good approximation of relative risk in this case? Assume there was no incident density sampling.

Adverse outcome cases

Adverse outcome controls

Exposed/carrier

506 

12630

Unexposed/non-carrier

1499 

42680 

2. We are interested in not only the effect of the genotype but also of age on the risk of severe COVID-19 outcomes. Calculate the odds ratio of adverse outcomes associated with being > 60 years old using the 2×2 table below. Is it a good approximation of relative risk in this case? You already know there was no incident density sampling in this study.

Adverse outcome cases

Adverse outcome controls

Exposed/60+

1538

37686

Unexposed/60 or under

467 

17624

Extra credit: For questions 1 and 2, would you use the crude OR that you estimated, or additionally adjust it for potential confounders– if so, which ones?

3. What is the proportion of the risk of death/severe respiratory failure among the exposed that is attributable to being a carrier of this mutation? Show your work and interpret your finding. State the assumption you need to make in your interpretation.

4. What is the proportion of the risk of death/severe respiratory failure among the exposed that is attributable to being older than 60 years of age? Show your work and interpret your finding. State the assumption you need to make in your interpretation.

5. Based on these data only, which factor– genetics or age>60– should public health professionals and clinicians focus on more to identify individuals at a higher risk for dying or developing severe respiratory failure due to COVID-19?