Here’s how I’m thinking about it (still digging into the details): across genomics, it’s become clear few traits have clear traceability to a few loci in the genome.

Instead, evidence has been growing that epistasis, the nonlinear interaction between genes and other genomic regions, predominates in explanations of most phenotypes.

What this paper does is show where upstream of the genome various combinations of mutations can interact to cause damage during development, thus leading to the phenotype. Rather than correcting a particular mutation, or targeting drugs to their protein products, we may find downstream protein-protein interactions that are strong drivers of the phenotype, and hopefully find ways to prevent/reverse these effects.