I would like to lay out why this work is scientifically unsound and problematic. Note that my PhD was in a genetics/informatics lab, and I spent time working with population geneticists. This is a thread. #MedTwitter https://twitter.com/JAMA_current/status/1304102350857154567

One of the mistakes of my early training was conflating race and genetics. This is still done at every level of medicine and science. Race is a SOCIAL construct. It is not based on biology. Race is not a risk factor; racism is.

When you take a group of people of the same "race" and look at their genetics, it's incredibly diverse because again, race as a social construct is not capturing underlying biology, genetic ancestry. Race isn't biological.

Differences in genetic ancestry can affect differences in gene expression. You would need to actually genotype or sequence people and pair that information with differences in gene expression. Then you could say "people with this genetic variant are at higher or lower risk".

So this paper is methodologically unsound because the genetic differences within each self identified "racial" group could be as different as between groups. Because race is not biological. This paper shouldn't even be written.

But what's even more problematic is the lack of funding and effort to understand the role racism has played in COVID outcomes. Socioeconomic disparities and lack of access to care due to racist policies are known to affect health outcomes.

I leave you with the wise words of @AdeAdamson https://twitter.com/AdeAdamson/status/1304515976369762304?s=20

Since the entire study design was fundamentally flawed to begin with, I decided not to address the small sample size, the fact that gene expression doesn't always correlate with protein expression, and that we have no proof that TMPRSS2 expression has any effects on mortality.

Additional reading:
https://science.sciencemag.org/content/351/6273/564.summary https://www.ncbi.nlm.nih.gov/pmc/articles/PMC515312/

Required reading for all reviewers and journal editors: https://twitter.com/RheaBoydMD/status/1278732668469800960?s=20

This is a valid point. Gene expression is influenced by the environment, but also influenced by underlying genetics. However, it was never made explicit that by using gene expression + race, they were focusing on environmental determinants. https://twitter.com/elizabethmatsui/status/1305166271386914816?s=20

Since I've seen so many in my field use gene expression as a proxy for underlying genetic differences (recognizing that environment plays a role, but hand waving its impact), this was my reading of it since it wasn't explicitly stated.

There are so many studies focusing on how genetic variation influences gene expression; far less on the role of the environment. Since most of medicine still treats race as biological, without it being explicitly stated otherwise here, I believe the paper perpetuates that notion.

I do not think the authors were explicitly trying to push for biological race. Rather, I think that the notion of biological race is ingrained in medicine despite being refuted over and over again. It’s a harmful notion, and it was how I was taught as well.

And to clarify, I do think we need genetic studies across diverse ancestries. Traditionally, most studies have focused on European ancestral populations, which does not capture the full range of human genetic diversity.