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Survived another ASHG plenary talk :)
In case you missed it, I presented results on behalf of @Regeneron from a trans-ancestry #COVID19 meta-analysis of common and rare variants + gene burden tests in >883k imputed samples and >592k exomes.
#ASHG20
In case you missed it, I presented results on behalf of @Regeneron from a trans-ancestry #COVID19 meta-analysis of common and rare variants + gene burden tests in >883k imputed samples and >592k exomes.
#ASHG20
Using REGENIE developed by @joellembatchou and @marchini (SAIGE gave us some bizarre results with rare variants) to run our common and rare variant GWASes, we found 2 loci associated with susceptibility and 3 loci with hospitalization. #ASHG20
Curiously, despite losing ~75% of the cases, we found more loci with hospitalization than using all COVID19 positive individuals - @covid19_hgi sees the same pattern.
One might suspect a severe COVID19 GWAS would be even more powerful at the same sample size
#ASHG20
One might suspect a severe COVID19 GWAS would be even more powerful at the same sample size
#ASHG20
Unlike our common var GWAS, our rare variant analysis was flat across the board - most likely because we only have 1108 hospitalized cases in the exome data compared to 3539 cases in the GWAS data. Similar situation with burden tests. #ASHG20
However, we are looking forward to collaborating with @covid19_hgi to run WES/WGS meta-analyses and hopefully identify some rare variants and genes in the future! #ASHG20
There are a few published #COVID19 exome seq studies, most notably Zhang et al @ScienceMagazine - that reported a rare LoF burden in 13 TLR3- and IRF7-dependent type I IFN genes (659 cases & 534 controls). https://science.sciencemag.org/content/370/6515/eabd4570
Given ~2x the cases and >17x the controls, we should be well-powered to replicate this biologically attractive hypothesis!
Sadly, our #replication failed despite testing 1) just pLoFs or pLoFs+missense, 2) 3 different AF thresholds, or 3) focusing on only severe COVID19
#ASHG20
Sadly, our #replication failed despite testing 1) just pLoFs or pLoFs+missense, 2) 3 different AF thresholds, or 3) focusing on only severe COVID19
#ASHG20
In the spirit of #openscience, we've made the #COVID19 exome summary statistics for the UKB 450k freeze publicly available ( https://rgc-covid19.regeneron.com/ ) and hope to release the rest of the exome summary stats soon :)
#ASHG20
#ASHG20
Huge thanks to everyone who contributed to this analysis (and big thanks
to @jdbackman who did fantastic exome QC) and all the contributing studies: @uk_biobank, @PennMedicine Biobank, @ancestrydna, & GHS + @FinnGen_FI and @GenomiccStudy who made their sumstats public.
to @jdbackman who did fantastic exome QC) and all the contributing studies: @uk_biobank, @PennMedicine Biobank, @ancestrydna, & GHS + @FinnGen_FI and @GenomiccStudy who made their sumstats public.
Also, for those #phd students out there, don't let someone tell you that you'll never get an ASHG plenary talk if you leave academia. People can be mean and I was a fool to believe them when I was younger.
