Abstract 16609: Obstructive Sleep Apnea and 4q25 Genotype are Associated With Atrial Fibrillation Independent of Traditional Risk Factors

Introduction: Obstructive sleep apnea (OSA) and common single nucleotide polymorphisms (SNPs) at the 4q25 locus are associated with increased risk of atrial fibrillation (AF). Whether these associations are independent of traditional contributors to AF is unknown. Hypothesis: The associations of OSA severity and 4q25 genotype with prevalent AF persist after adjustment for established AF risk factors. Methods: Using billing code queries, key word searches, and manual chart review, we assembled from BioVU, a Vanderbilt Medical Center resource linking DNA samples to de-identified electronic health records, a cohort of all adults with overnight polysomnography performed in our Sleep Lab and at least one formal 12-lead electrocardiogram (EKG). Case status was defined by electrocardiographic data in support of AF (EKG, ambulatory monitoring, pacemaker/defibrillator interrogation) 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 narrative portions of the medical record. OSA severity was categorized as none, mild, moderate, or severe based on the reported apnea-hypopnea index. Genotyping of 4q25 SNPs (rs2200733, rs10033464) was performed using the Sequenom platform. Logistical regression was used to test for association between AF status, OSA category, and 4q25 genotype; each model contained a single SNP. Age, gender, body mass index, ethnicity, hypertension status, and heart failure status were included as co-variates. Results: The cohort consisted of 674 patients (62 ± 13 years; 44% female), including 132 with AF. After adjustment for established risk factors, the association between AF and OSA severity was borderline significant (OR 1.2, 95% CI 1.0-1.5); the association between AF and 4q25 genotype was more robust (OR 3.5, 95% CI 2.2-3.5 [rs2200733]; OR 3.2, 95% CI 2.1-5.0 [rs10033464]). Conclusions: OSA status and 4q25 genotype are associated with AF status independent of standard clinical characteristics and each other. Knowledge of 4q25 genotype may enhance AF risk-stratification for those undergoing polysomnography.