To what extent gene connectivity within co-expression network matters for phenotype prediction?

Recent literature on the differential role of genes within networks distinguishes core from peripheral genes. If previous works have shown contrasting features between them, whether such categorization matters for phenotype prediction remains to be studied. We sequenced RNA in a collection and built co-expression networks to define core and peripheral genes. We found that cores were more differentiated between populations than peripherals while being less variable, suggesting that they have been constrained through potentially divergent selection. We also showed that while cores were overrepresented in a subset of genes deemed important for trait prediction, they did not systematically predict better than peripherals or even random genes. Our work is the first attempt to assess the importance of co-expression network connectivity in phenotype prediction. While highly connected core genes appear to be important, they do not bear enough information to systematically predict better quantitative traits than other gene sets.