A current challenge in interpretation of genome-wide association studies is to establish the mechanistic links between the measured genotype and observed phenotype. The integration of gene expression with disease genome-wide association studies is emerging as an important strategy for deciphering these regulatory mechanisms. For renal disease, the availability of both tissue- and disease-specific expression data makes the strategy a compelling option. In this review, three approaches of integrating single nucleotide polymorphism (SNP) genotypes with transcriptional regulation are discussed as follows: (1) interpreting the functional role of transcripts affected by a SNP, (2) identifying the mechanistic role of noncoding SNPs in regulation, and (3) identifying regulatory candidate SNPs with expression associations. Combining these strategies in an integrative manner should allow the discovery of more extensive regulatory information. Linking genetics to systems biology more directly promises the opportunity to explain how genetic variants contribute to disease in a truly holistic manner.