We describe here the design and initial implementation of the eMERGE-PGx project. eMERGE-PGx, a partnership of the eMERGE and PGRN consortia, has three objectives : 1) Deploy PGRNseq, a next-generation sequencing platform assessing sequence variation in 84 proposed pharmacogenes, in nearly 9,000 patients likely to be prescribed drugs of interest in a 1–3 year timeframe across several clinical sites; 2) Integrate well-established clinically-validated pharmacogenetic genotypes into the electronic health record with associated clinical decision support and assess process and clinical outcomes of implementation; and 3) Develop a repository of pharmacogenetic variants of unknown significance linked to a repository of EHR-based clinical phenotype data for ongoing pharmacogenomics discovery. We describe site-specific project implementation and anticipated products, including genetic variant and phenotype data repositories, novel variant association studies, clinical decision support modules, clinical and process outcomes, approaches to manage incidental findings, and patient and clinician education methods.

Background Based on studies with limited statistical power, lipoprotein(a) [Lp(a)] is not considered a risk factor for cardiovascular disease (CVD) in African Americans. We evaluated associations between Lp(a) and incident CVD events in African Americans and Caucasians in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results Plasma Lp(a) was measured in African Americans (n=3,467) and Caucasians (n=9,851). Hazards ratios (HRs) for incident CVD events (coronary heart disease [CHD] and ischemic strokes) were calculated. Lp(a) levels were higher with wider interindividual variation in African Americans (median [interquartile range]: 12.8 [7.1–21.7] mg/dl) than Caucasians (4.3 [1.7–9.5] mg/dl; p <0.0001). At 20 years of follow-up, 676 CVD events occurred in African Americans and 1,821 events occurred in Caucasians. Adjusted HRs (95% confidence interval [CI]) per race-specific 1-SD–greater log-transformed Lp(a) were 1.13 (1.04–1.23) for incident CVD, 1.11 (1.00–1.22) for incident CHD, and 1.21 (1.06–1.39) for ischemic strokes in African Americans. For Caucasians, the respective HRs (95% CIs) were 1.09 (1.04–1.15), 1.10 (1.05–1.16), and 1.07 (0.97–1.19). Quintile analyses showed that risk for incident CVD was graded but statistically significant only for the highest compared with the lowest quintile (HR [95%CI] 1.35 [1.06–1.74] for African Americans; HR 1.27 [1.10–1.47] for Caucasians). Similar results were obtained using Lp(a) cut-offs of ≤10 mg/dl, >10–≤20 mg/dl, >20–≤30 mg/dl, and >30 mg/dl. Conclusions Lp(a) levels were positively associated with CVD events. Associations were at least as strong, with a larger range of Lp(a) concentrations, in African Americans compared with Caucasians.