Figure 1.

Study design. In this two-stage whole-exome sequencing study of DKD, an extreme case–control study design was adopted by leveraging 4372 participants of the Chronic Renal Insufficiency Cohort (CRIC) and Atherosclerosis Risk in Communities (ARIC) studies in the stage-1 analysis. Participants with DKD from the CRIC study were compared with one primary and two secondary control groups without DKD from the ARIC study. Suggestive signals identified in the stage-1 WES study were confirmed among 11 487 Trans-Omics for Precision Medicine (TOPMed) participants with existing WGS data (stage-2). Signals achieving an exome-wide significance based on Bonferroni correction in the meta-analysis were reported.