Abstract 11495: Genetic Loci Associated With Atrial Fibrillation Have Limited Relation to Left Atrial Structure in the Framingham Heart Study
Background: Left atrial (LA) structure and function are intermediate phenotypes for atrial fibrillation (AF) risk. Genome-wide association studies (GWAS) have identified novel genetic loci related to AF. To date, 11 AF-associated, single nucleotide polymorphisms (SNPs) have been replicated. We hypothesized that SNPs related to AF would be associated with measures of LA structure as assessed by transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR) in a community-based cohort.
Methods: We investigated the associations between identified SNPs and atrial structure in the Framingham Heart Study. SNPs were selected from large GWAS and significant relations to AF following Bonferroni correction (P<5.0x10-8). TTE LA dimension was determined by M-mode in Offspring (1995-1998) or Generation 3 (2002-2005) cohort participants. LA volume by CMR was determined using biplane stead state free precession among Offspring participants (2002-2006). The primary analysis consisted in linear regression relating the SNPs to measures of LA structure.
Results: The cohort included 6861 participants with TTE (mean age 48±13 years, 52% women) and 1555 participants with CMR (mean age 60±9 years, 53% women). LA measures were 38.2±5.3 mm by TTE and 73.5±23.8 mL by CMR. Two SNPs on chromosome 4 in proximity to the PITX2 gene were significantly related to LA volume by CMR (see Table). However, the significance was attenuated by indexing LA volume to body surface area. No SNPs were related to TTE linear LA dimension.
Conclusion: In a community-based cohort, we found limited associations between selected SNPs associated with AF and measures of LA structure. Further investigation with larger cohorts and a broader array of SNPs may be necessary to determine the relation between genetic loci associated with AF and atrial structure. Examining such relations may inform the genetics and pathogenesis of AF.
- © 2013 by American Heart Association, Inc.