title: Relation of Obstructive Sleep Apnea and a Common Variant at Chromosome 4q25 to Atrial Fibrillation.
abstract: Obstructive sleep apnea (OSA) and single nucleotide polymorphisms (SNPs) at the 4q25 locus are associated with increased risk of atrial fibrillation (AF). Whether these associations are independent of traditional risk factors for AF remains unknown. Using billing code queries and manual chart review, we assembled a cohort of adults that underwent overnight polysomnography and at least 1 12-lead electrocardiogram. Case status was defined by electrocardiographic data in support of AF or documentation of AF by a staff cardiologist. Controls were defined by a lack of primary evidence of AF and absence of a diagnosis of AF in the medical record. OSA severity was categorized based on Apnea-Hypopnea Index. Genotyping for a key 4q25 SNP (rs2200733) was performed using the Sequenom platform. Logistic regression was used to test for associations of AF with OSA category and 4q25 SNP genotype while adjusting for age, gender, body mass index, ancestry, hypertension status, and heart failure status. The cohort consisted of 674 subjects (62 ± 13 years; 44% women), including 132 patients with AF. After adjustment for established risk factors, the association between AF and OSA severity was borderline significant (odds ratio 1.2, 95% CI 1.0 to 1.5). The association between AF and 4q25 SNP status remained significant in a fully adjusted model that included OSA severity (odds ratio 1.5, 95% CI 1.3 to 5.7). In conclusion, OSA severity and the chromosome 4q25 SNP genotype were associated with AF status independent of clinical risk factors. Knowledge of AF-related SNPs may enhance AF risk stratification for those undergoing polysomnography.
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt Medical Center, Nashville, Tennessee.
authors.forename: Neel J
authors.initials: NJ
authors.lastname: Patel
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt Medical Center, Nashville, Tennessee.
authors.forename: Quinn S
authors.initials: QS
authors.lastname: Wells
authors.affiliation: Department of Biostatistics, Vanderbilt Medical Center, Nashville, Tennessee.
authors.forename: Shi
authors.initials: S
authors.lastname: Huang
authors.affiliation: Division of Sleep Medicine, Department of Neurology, Vanderbilt Medical Center, Nashville, Tennessee.
authors.forename: Raghu P
authors.initials: RP
authors.lastname: Upender
authors.affiliation: Division of Cardiology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Dawood
authors.initials: D
authors.lastname: Darbar
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt Medical Center, Nashville, Tennessee. Electronic address: ken.monahan@vanderbilt.edu.
authors.forename: Ken
authors.initials: K
authors.lastname: Monahan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017286:Polysomnography; D012307:Risk Factors; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology*