A new paper digs into OAS1, A prenylated dsRNA sensor protects against severe COVID-19:
Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response.
You can find the SNP in you 23andMe raw data (unless you are on the recent chip; I looked for a tag variant but found none). If I’m reading the paper correctly, having the AA genotype increases your risk of severe COVID-19 by an odds of 1.58, all things equal. Not crazy bad, but not great either. The haplotype that carries the G allele in non-Africans seems to come from Neanderthals. In Africa, the ancestral G is the majority, though a minority of individuals are A, and that was passed on to Eurasians.
Here is a plot for the 1000 Genomes populations.
One thing I immediately noticed is that Peruvians have the highest frequency of the A allele in the dataset. Peru has had the highest COVID-19 death rate in the world, and its frequency of A means that a great number of people will be AA (the frequency of A squared).
I looked in Anders Bergstrom’s HGDP whole-genome data and found an interesting pattern in the frequencies of the G alelle:
Three of the four populations with no copies of the protective G allele are indigenous to the Americas. The Maya, who are known to have European admixture, also have very low frequencies of the G allele. Now, it is true that East Asians also have low frequencies of the G allele (the Yakuts also lack it, so perhaps this was ancestral to Siberians?), but they may have other protective variants (or, suffered through an earlier coronavirus epidemic). I think OAS1 may turn out to be one of the loci that could be associated with a higher risk to severe COVD-19 in the New World.