We note that while lack of enrichment of associations with T2D and related-traits does not provide support for a causal connection, it does not eliminate the possibility that individual genes could still be found to have a genetic effect and thus be instrumental to T2D predisposition. For example, the absence of enrichment in the OXPHOS genes does not disprove the association to T2D of one of its genes, C8orf38 (an assembly factor in Complex I, the first complex in the mitochondrial electron transfer chain; Entrez ID 137682) [22], which lies near a validated T2D SNP found in the recent DIAGRAM+ T2D meta-analysis [36], but it does not provide further support for C8orf38 being causal.
