BioVU accrues DNA samples extracted from blood remaining from routine clinical testing after they have been retained for 3 days and are scheduled to be discarded. A full description of this resource and its associated ethical, privacy and other protections has been published elsewhere (Roden et al., 2008 (link)). All patients age ≥18 years with an outpatient laboratory draw, who have a signed consent to treatment form, and that have not made a formal indication to opt-out are potential inclusions in BioVU. The resource is linked to a de-identified version of the EMR called the synthetic derivative (Roden et al., 2008 (link)). As of January 18, 2010, the resource included 75 769 DNA samples.
The study population consisted of the first ∼6000 European–Americans accrued into BioVU. The only selection criteria were that they met the general conditions for eligibility for BioVU; no clinical inclusion or exclusion criteria were applied. In the current analysis, we selected five SNPs with previously known disease associations: rs1333049 [coronary artery disease (CAD) and carotid artery stenosis (CAS)], rs2200733 [atrial fibrillation (AF)], rs3135388 [multiple sclerosis (MS) and systemic lupus erythematosus (SLE)], rs6457620 [rheumatoid arthritis (RA)], and rs17234657 [Crohn's disease (CD)]. (Some other potential associations exist for some SNPs, such as progression of carotid atherosclerosis and rs1333049, but are not represented well through ICD9 codes.) The primary outcome of this study was identification of the prior statistical associations with MS, CD, AF, CAD, SLE, CAS and RA.
Genotyping was conducted by the Vanderbilt DNA Resources Core using the mid-throughput Sequenom® genotyping platform (rs1333049, rs3135388 and rs17234657; genotyping efficiency 98.4–100%), which is based on a single base primer extension reaction coupled with mass spectrometry, or using a TaqMan assay (rs6457620 and rs2200733; genotyping efficiency 99.4% and 99.0%, respectively). Quality control procedures included examination of marker and sample genotyping efficiency, allele frequency calculations and tests of Hardy–Weinberg equilibrium.
The study population consisted of the first ∼6000 European–Americans accrued into BioVU. The only selection criteria were that they met the general conditions for eligibility for BioVU; no clinical inclusion or exclusion criteria were applied. In the current analysis, we selected five SNPs with previously known disease associations: rs1333049 [coronary artery disease (CAD) and carotid artery stenosis (CAS)], rs2200733 [atrial fibrillation (AF)], rs3135388 [multiple sclerosis (MS) and systemic lupus erythematosus (SLE)], rs6457620 [rheumatoid arthritis (RA)], and rs17234657 [Crohn's disease (CD)]. (Some other potential associations exist for some SNPs, such as progression of carotid atherosclerosis and rs1333049, but are not represented well through ICD9 codes.) The primary outcome of this study was identification of the prior statistical associations with MS, CD, AF, CAD, SLE, CAS and RA.
Genotyping was conducted by the Vanderbilt DNA Resources Core using the mid-throughput Sequenom® genotyping platform (rs1333049, rs3135388 and rs17234657; genotyping efficiency 98.4–100%), which is based on a single base primer extension reaction coupled with mass spectrometry, or using a TaqMan assay (rs6457620 and rs2200733; genotyping efficiency 99.4% and 99.0%, respectively). Quality control procedures included examination of marker and sample genotyping efficiency, allele frequency calculations and tests of Hardy–Weinberg equilibrium.
