🎉Final version of our dosage sensitivity study out today @CellCellPress!
cell.com/cell/fulltext/…

Explored CNV associations across 54 phenotypes in ~1M genomes

Since @medrxivpreprint in 2021: added 200k samples & 22 phenotypes thanks to @GeneDx @ESTbiobank @vumcdbmi

🧵👇

1/6 1. We compared effects of rare CNVs (rCNVs) across 54 disorders

Known genomic disorder (GD) CNVs increase risk for basically all (90%) diseases we assessed

Similar for rCNVs of constrained genes outside known GDs, but:
- Weaker effects than GDs
- Fewer associated diseases

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🔊New @biorxivpreprint from the @TalkowskiLab🔊

Important work by @Xuefang6 digging into details of SVs from short/long-read genomes on matched samples.

She asked: where do @illumina & @PacBio SV calls overlap, where don't they, and why?

Thread 👇

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biorxiv.org/content/10.110… For deletions:

- In the 90% least repetitive regions of the genome, vast majority of technology-unique deletions (for both Illumina & Pac Bio) are false positives.

- After controlling FDR at 5% per tech., the remaining calls are ~identical between Ill. & PB (93.8% overlap)

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Careful benchmarking of ~70 different methods for SV detection from human genomes:
genomebiology.biomedcentral.com/articles/10.11…

Looks to be an impressively comprehensive and valuable reference to guide future SV discovery efforts.

Thank you to the authors for compiling this study!! FWIW, our own conclusions from other data broadly agree with this analysis:

1. No single algorithm is sufficient
2. Integrating multiple algs is critical
3. Some combos have better synergy than others
4. Mixing evidence types (e.g., one PE/SR alg, one depth alg, etc) is best

At long last, our WGS association study in autism quartets is live @NatureGenet :
nature.com/articles/s4158…

Several points worth emphasizing from this paper.

Twitter explainer below 👇, also great N&V piece by Wray & Gratten here:
nature.com/articles/s4158…

1/15 First and most importantly: huge multi-year collaboration b/t @TalkowskiLab & many others.

Particular congrats to @DonnaWerling, Harrison, @joonomics, @m_sto, and Lingxue, who spearheaded the analyses from start to finish!

Now, on to the science...

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