Document Detail


Identification of genomic predictors of atrioventricular conduction: using electronic medical records as a tool for genome science.
MedLine Citation:
PMID:  21041692     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Recent genome-wide association studies in which selected community populations are used have identified genomic signals in SCN10A influencing PR duration. The extent to which this can be demonstrated in cohorts derived from electronic medical records is unknown.
METHODS AND RESULTS: We performed a genome-wide association study on 2334 European American patients with normal ECGs without evidence of prior heart disease from the Vanderbilt DNA databank, BioVU, which accrues subjects from routine patient care. Subjects were identified by combinations of natural language processing, laboratory queries, and billing code queries of deidentified medical record data. Subjects were 58% female, of mean (± SD) age 54 ± 15 years, and had mean PR intervals of 158 ± 18 ms. Genotyping was performed with the use of the Illumina Human660W-Quad platform. Our results identify 4 single nucleotide polymorphisms (rs6800541, rs6795970, rs6798015, rs7430477) linked to SCN10A associated with PR interval (P=5.73 × 10(-7) to 1.78 × 10(-6)).
CONCLUSIONS: This genome-wide association study confirms a gene heretofore not implicated in cardiac pathophysiology as a modulator of PR interval in humans. This study is one of the first replication genome-wide association studies performed with the use of an electronic medical records-derived cohort, supporting their further use for genotype-phenotype analyses.
Authors:
Joshua C Denny; Marylyn D Ritchie; Dana C Crawford; Jonathan S Schildcrout; Andrea H Ramirez; Jill M Pulley; Melissa A Basford; Daniel R Masys; Jonathan L Haines; Dan M Roden
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-01
Journal Detail:
Title:  Circulation     Volume:  122     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2012-01-10     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2016-21     Citation Subset:  AIM; IM    
Affiliation:
Office of Personalized Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0575, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Databases, Nucleic Acid*
Electrocardiography*
Electronic Health Records*
Female
Genome-Wide Association Study
Genotype
Heart / physiopathology*
Humans
Male
Middle Aged
NAV1.8 Voltage-Gated Sodium Channel
Polymorphism, Single Nucleotide*
Sodium Channels / genetics*
Grant Support
ID/Acronym/Agency:
1 UL1 RR024975/RR/NCRR NIH HHS; KL2 RR024977/RR/NCRR NIH HHS; KL2 TR000446/TR/NCATS NIH HHS; TL1 RR024978/RR/NCRR NIH HHS; TL1 TR000447/TR/NCATS NIH HHS; U01 HG004603-04/HG/NHGRI NIH HHS; U01 HG04603/HG/NHGRI NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 RR024975-02/RR/NCRR NIH HHS; UL1 TR000445/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/NAV1.8 Voltage-Gated Sodium Channel; 0/SCN10A protein, human; 0/Sodium Channels
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Bundle-branch block morphology and other predictors of outcome after cardiac resynchronization thera...
Next Document:  Titin is a target of matrix metalloproteinase-2: implications in myocardial ischemia/reperfusion inj...