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Today we're sharing an analysis of the genetics behind two important COVID-19 genes: ACE2 and TMPRSS2. A thread on what we have found 1/9
https://www.medrxiv.org/content/10.1101/2020.04.22.20074963v1 @LifelinesNL @serenasanna1
https://www.medrxiv.org/content/10.1101/2020.04.22.20074963v1 @LifelinesNL @serenasanna1
ACE2 and TMPRSS2 are necessary for COVID-19 infection because they allow it to enter the cell (ACE2) and for the maturation of the virus (TMPRSS2) so that the virus can infect other cells 2/9
We are interested in the genetic effects in and around these genes, which may explain COVID-19 severity. Spoiler alert: we did not find much. But we think it's valuable to share these results as it reduces the amount of parallel investigations 3/9
We feel that sharing these null results is important, as the COVID-19 pandemic moves very fast. Scientists and clinicians need accurate information sooner rather than later. Even when better and larger scale studies are being set up 4/9
Why did we look for genetic effects around these genes? We are seeing differences in COVID-19 severity across different countries, age groups and sexes. Therefore we wondered if there was any genetic basis for these differences 5/9
What did we do? We looked for genetic associations in- and around the ACE2 and TMPRSS2 genes with 178 quantitative phenotypes (including cytokines and cardiometabolic biomarkers) and usage of 58 drug classes. This data is from the lifelines cohort of 36,339 individuals 6/9
What did we find? No associations pass our multiple testing thresholds. Our results on the quantitative traits are not easily linkable to COVID-19 severity. There is some biologically plausible evidence for variants affecting medication usage. 7/9
We find suggestive evidence that genetic polymorphisms around the ACE2 gene can influence medication use that can be linked to COVID-19 severity: antihypertensives and non steroid anti-inflammatory agents. Which is in line with comorbities of patients with severe COVID-19 8/9
Again, we don't find significant results, but the medication use may warrant further follow up. If you are interested in all the traits we tested, all our results can be found at https://covid19research.nl and in the manuscript https://www.medrxiv.org/content/10.1101/2020.04.22.20074963v1 9/9
A big thank you to all our collaborators, lifelines participants, @LifelinesNL @wijmenga_cisca @LudeFranke @serenasanna1 and Esteban Lopera for getting this out so fast!
