Figure 1.

Study design and workflow. Step 1: to identify novel loci for increased risk of diabetes cardiovascular complications, we conducted a meta-analysis of two GWAS for CHD in Chinese patients with T2D. We followed up the top signals in an additional cohort of Chinese patients with T2D and further performed replication in multiple populations. Finally, the PDE1A locus was identified. Step 2: to understand the pleiotropy and the underlying biological function of the PDE1A locus, we examined this locus in associations with 1) seven types of diabetes cardio-renal complications using two different study designs (i.e., case-control and prospective designs) and 2) a wide spectrum of phenotypes using the publicly available data. We also performed bioinformatic analyses for the PDE1A locus, including the eQTL analysis, and the transcriptome-wide association study. Step 3: to explore the potential clinical utility of personal genetic information, we investigated the effect of each ABC goal on diabetes cardiovascular risk according to different genotypes of PDE1A rs10171703. CHF, congestive heart failure; GIANT, Genetic Investigation of ANthropometric Traits; MAF, minor allele frequency; UKB, UK Biobank.