Thread by @DrEricDing

GOOD news—if you have certain Neanderthal DNA 🧬 & get #COVID19. People with certain Neanderthal genes on chromosome 12 have lower rates of ICU. This region encodes proteins that activate enzymes that are important during infections with RNA viruses.
pnas.org/content/118/9/…

2) That said, another Neanderthal gene is bad. “Recently, it was shown that a haplotype in a region on chromosome 3 is associated with becoming critically ill upon infection with #SARSCoV2 and was contributed to modern humans by Neanderthals”.

3) For this new finding, “a haplotype on chromosome 12, which is associated with a ∼22% reduction in relative risk of becoming severely ill with #COVID19, is inherited from Neandertals. This haplotype is present at substantial frequencies in all regions of 🌎 outside Africa.”

4) Neanderthals “are likely to have adapted to infectious diseases, which are known to be strong selective factors that may, at least partly, have differed between sub-Saharan Africa and Eurasia” pnas.org/lookup/externa…

5) “Indeed, several genetic variants contributed by archaic hominins to modern humans have been shown to affect genes involved in immunity. pnas.org/lookup/ijlink/…

6) variants at several loci containing genes involved in innate immunity come from Neandertals and Denisovans (15), for example, toll-like receptor gene variants which decrease the susceptibility to Helicobacter pylori infections and risk for allergies. pnas.org/lookup/externa…

7) Furthermore, proteins interacting with RNA viruses have been shown to be encoded by DNA regions introgressed from Neandertals more often than expected. pnas.org/lookup/externa…

8) Regarding the other Neanderthal gene on chromosome 3 that increased respiratory failure, nejm.org/doi/full/10.10…, was contributed by Neanderthals according to scientists.

9) For this current study that was protective, “the index variant of the protective haplotype in the GenOMICC study (rs10735079) matches all three Neandertal genomes available. The relative risk of needing ICU is reduced by ∼22% per copy of the Neandertal haplotype (OR= 0.78)”

10) the G allele of the index variant “rs10735079” is lower in Africans and certain Asian populations, and much more common in Europe (as expected in Neanderthals), but its still quite dispersed. ncbi.nlm.nih.gov/snp/rs10735079…

11) As for the other bad Neanderthal gene on chromosome 3 (sorry I’m skipping around), found in the NEJM paper above, it is best indexed by the single nucleotide polymorphism (SNP) called “rs35044562”. nature.com/articles/s4158…

12) Fortunately, this other bad Neanderthal risk gene 🧬 on chromosome 3, indexed by “re35044562” is really really rare. The alternative allele (the variant), has extremely low frequencies. But higher in Europeans (naturally), but only a low 8%. ncbi.nlm.nih.gov/snp/rs35044562…

13) but wait, this bad one is common in South Asians with 37%—But it mostly comes from one major study it seems which only has 974 South Asians. Unsure if generalizable

14) also in a very small 290 person study of Ashkenazi Jewish population, this bad risk gene had a 12.8% frequency.

15) Okay, I’m realizing genetics is not well understood by most people. So a haplotype is a genetic configuration of gene(s)— often index by a polymorphism- a mutation that is marking some underlying gene(s) in its nearby region. nature.com/scitable/defin…

16) Sometime when we are doing a GWAS (genome wide association study), they genome scan across person’s entire genome by plucking SNPs (single nucleotide polymorphism- mutations) that represent each region well. And then check with SNPs show association with a disease outcome.

17) That’s what they did in the NEJM study. They found certain genes an some SNPs associated with hospitalization for respiratory failure on certain chromosomes. nejm.org/doi/full/10.10…

18) Sometimes a SNP falls in a known gene, but sometimes it falls in a less familiar region, but because the SNPs are correlated with many other mutations (polymorphisms if mutation is common), it could represent something else nearby that affects risk. nature.com/articles/s4158…

19) That’s why sometimes SNPs are called “haplotype tagging SNPs” in that they “tag” something going on affecting risk of disease in the nearby regional area. So even if we don’t know precisely what exactly, the SNP-&-disease study still tells us it’s linked with higher risk!!

20) So you can’t just rely on that 23andMe tells you that you have some Neanderthal genes, you need to know which ones you have. 23andMe doesn’t release all data without lots of robustness checks and validations for new disease risks, so they don’t release to you all risk data.