These hypotheses could be tested using a Gene Set Enrichment Analysis (GSEA) approach applied to genetic variant association data [23]. We originally described GSEA to test whether predefined biological processes or gene sets are enriched for genes with coordinate modest expression differences between two samples, differences that are hard to detect when inspecting each gene separately [9], [24]. In fact, GSEA was first used to show that OXPHOS genes are collectively downregulated in human muscle in diabetic compared to non-diabetic individuals [9].
