DNA repository linked to EMR finds genes associated with PR interval
Special algorithms allowed researchers to successfully search an EMR-derived cohort to help confirm and newly identify genes associated with the PR interval, according to a study published online Nov. 1 in Circulation.
Joshua C. Denny, MD, and colleagues from Vanderbilt University School of Medicine in Nashville, Tenn., reported that recent genome-wide association studies of the PR interval converged on variants in SCN10A.
"Interestingly, SCN10A is located on chromosome 3 adjacent to SCN5A, which encodes the major cardiac sodium channel gene in the heart, but SCN10A had not, to date, been implicated as a modulator of cardiovascular physiology," they wrote.
Unlike previous studies, which relied on the analysis of large cohorts of patients recruited from communities or specific clinics for epidemiological study, Denny et al. sought an alternate strategy, "in which DNA repositories are linked to EMRs across large healthcare systems."
While these linked repositories might have theoretical advantages, "such as rapid generation of patient sets for study and the ability to study large numbers of subjects accrued without bias with respect to factors such as disease or age ... the utility of EMR-based approaches for validation or discovery of genotype-phenotype associations in populations remains largely unexplored."
In that regard, researchers created algorithms to identify patients with normal ECGs without evidence of prior heart disease from the Vanderbilt DNA databank, BioVU, which accrues subjects from routine patient care. The genome-wide association study found 2,334 European American patients that fit the algorithm, out of a database of nearly 85,000 patients.
Subjects were 58 percent female, mean age 54 years and had mean PR intervals of 158 ms. Genotyping was performed with the use of the Human660W-Quad platform (Illumina).
Researchers identified four single nucleotide polymorphisms (rs6800541, rs6795970, rs6798015, rs7430477) linked to SCN10A associated with PR interval. Three of these had previously been implicated in other research, one was not.
"We demonstrate that a population identified by interrogation of a deidentified version of an EMR system that has been organized for research purposes can be used to efficiently identify genomic determinants of PR interval," they concluded.
"The generalizability of any result such as this, from an EMR or other source such as a community cohort or a clinical trial, may be limited if the recruitment is in some fashion biased. The fact that we identify a locus implicated in recent genome-wide association study analyses speaks further to the generalizability of this result," they said.
Joshua C. Denny, MD, and colleagues from Vanderbilt University School of Medicine in Nashville, Tenn., reported that recent genome-wide association studies of the PR interval converged on variants in SCN10A.
"Interestingly, SCN10A is located on chromosome 3 adjacent to SCN5A, which encodes the major cardiac sodium channel gene in the heart, but SCN10A had not, to date, been implicated as a modulator of cardiovascular physiology," they wrote.
Unlike previous studies, which relied on the analysis of large cohorts of patients recruited from communities or specific clinics for epidemiological study, Denny et al. sought an alternate strategy, "in which DNA repositories are linked to EMRs across large healthcare systems."
While these linked repositories might have theoretical advantages, "such as rapid generation of patient sets for study and the ability to study large numbers of subjects accrued without bias with respect to factors such as disease or age ... the utility of EMR-based approaches for validation or discovery of genotype-phenotype associations in populations remains largely unexplored."
In that regard, researchers created algorithms to identify patients with normal ECGs without evidence of prior heart disease from the Vanderbilt DNA databank, BioVU, which accrues subjects from routine patient care. The genome-wide association study found 2,334 European American patients that fit the algorithm, out of a database of nearly 85,000 patients.
Subjects were 58 percent female, mean age 54 years and had mean PR intervals of 158 ms. Genotyping was performed with the use of the Human660W-Quad platform (Illumina).
Researchers identified four single nucleotide polymorphisms (rs6800541, rs6795970, rs6798015, rs7430477) linked to SCN10A associated with PR interval. Three of these had previously been implicated in other research, one was not.
"We demonstrate that a population identified by interrogation of a deidentified version of an EMR system that has been organized for research purposes can be used to efficiently identify genomic determinants of PR interval," they concluded.
"The generalizability of any result such as this, from an EMR or other source such as a community cohort or a clinical trial, may be limited if the recruitment is in some fashion biased. The fact that we identify a locus implicated in recent genome-wide association study analyses speaks further to the generalizability of this result," they said.