# No evidence that ACE2 or TMPRSS2 drive population disparity in COVID risks

## TL;DR

This paper challenges the idea that genetic differences in ACE2 and TMPRSS2 genes explain population disparities in COVID risks, showing that earlier claims were based on flawed data interpretation.

## Contribution

The paper identifies a sampling artifact in prior research and provides empirical evidence that other genetic loci are more significant for COVID risk than ACE2 and TMPRSS2.

## Key findings

- Earlier claims about ACE2 and TMPRSS2 variants driving population disparities in COVID risk were based on flawed data interpretation.
- Empirical evidence shows that other genetic loci have a more significant impact on personal COVID risks than ACE2 and TMPRSS2.
- Variation in ACE2 and TMPRSS2 is unlikely to exacerbate population disparities in the effects of more risk-informative loci.

## Abstract

Early in the SARS-CoV2 pandemic, in this journal, Hou et al. (BMC Med 18:216, 2020) interpreted public genotype data, run through functional prediction tools, as suggesting that members of particular human populations carry potentially COVID-risk-increasing variants in genes ACE2 and TMPRSS2 far more often than do members of other populations. Beyond resting on predictions rather than clinical outcomes, and focusing on variants too rare to typify population members even jointly, their claim mistook a well known artifact (that large samples reveal more of a population’s variants than do small samples) as if showing real and congruent population differences for the two genes, rather than lopsided population sampling in their shared source data. We explain that artifact, and contrast it with empirical findings, now ample, that other loci shape personal COVID risks far more significantly than do ACE2 and TMPRSS2—and that variation in ACE2 and TMPRSS2 per se unlikely exacerbates any net population disparity in the effects of such more risk-informative loci.