My first favourite GWAS of the year.
Here the authors derived >3k cellular morphological traits using microscopic images of iPSCs from 297 donors and studied their associations with common and rare variants. Amazing
biorxiv.org/content/10.1101/2023.01.09.522731v1
@soumya_boston @DrAnneCarpenter
In the rare variant analysis, the authors discovered three beautiful associations where pLOF burden results in big changes in cellular morphology.
For e.g.,
pLOF burden in WASF2 ( a gene critical for actin cytoskeleton formation) disrupts the shape of the cytoplasm of the iPSCs
pLOF burden in PRLR (prolactin receptor) disrupts the pattern of mitochondrial distribution around the organelles.
The advantage of identifying these associations in cell lines is that you can validate them by knocking out the genes in the same cell lines and observing the changes in the associated phenotype.
And that's what the authors did. Look at how impressively these cellular morphological phenotypes are altered when you knock out the genes.
It feels so great to see where the GWAS field is heading. As imaging and cellular assay technologies advance, these are the kind of phenotypes we will be GWASing in the coming years.
twitter.com/doctorveera/status/1603596231070175236?s=20&t=WE9PJlKTEfSVZiPNmGdiZg
With the ability to quantify traits at the level of individual cells derived from patients, imagine the kind of discoveries and insights we will be able to make.
Congrats to the authors for this amazing work 👏 👏