Gene Ontology Enrichment Analysis
None of the nominally significant genes among MA myelomeningocele
subjects overlapped with the genes from the EA subjects (Table 1).
However, gene ontologies from each gene set did overlap between
ethnicities. GO enrichment analysis revealed that the three GO terms
titled “cell-cell signaling by wnt”, “Wnt signaling pathway”, and
“Signaling by Wnt” were enriched in disrupted genes from both
populations. Enrichment of these broad terms were expected because the
original 523 genes were retrieved using the overarching “cell-cell
signaling by wnt” term. In other words, any subset of the original gene
list is likely to be enriched for terms that describe the general WNT
signaling pathway.
More interesting are the lower level, more specific GO terms that were
enriched in both populations’ signaling pathways. These shared
ontologies suggest a shared mechanism behind myelomeningocele in these
two ethnicities. The clearest example is negative regulation of the
canonical WNT/β-catenin component of WNT signaling. Also, myoblasts are
mentioned in two different GO terms, one from each population.
“WNT/β-catenin plays a crucial role in myoblast fusion” is enriched
among MA genes and “myoblast differentiation” is enriched in the EA
population. While these are technically two different terms, together
they suggest that disrupted genes in both ethnicities may be important
for myoblast function.
That said, many GO terms were only enriched in one or the other
population’s disrupted gene lists. So, while some mechanisms may be
shared, others may be unique to each ethnicity. The ontology terms
enriched in only the MA gene list largely pertain to PCP, whereas the
story is less clear for the EA ontology terms.
Another difference between populations can be seen in Fig 2B, where MA
subjects tended to have more disrupted genes than EA subjects. More
research is needed, but the discrepancy could help explain why the
prevalence of myelomeningocele among Mexicans is higher than in
non-Hispanic whites (Canfield et al., 2014).