rs11067773 (LINC02463): Atrial Fibrillation and PR Interval

Key takeaways

• rs11067773, located near LINC02463 (a long intergenic non-coding RNA, or lncRNA) and the adjacent pseudogene RN7SL865P, has been reported in large-scale GWAS studies as a potential contributor to atrial fibrillation (AF) risk
• This locus was also flagged in a GWAS of heart rate changes during and after exercise in approximately 67,000 UK Biobank participants
• A PR interval meta-analysis in over 92,000 individuals identified the same region, linking it to electrical conduction speed between the heart's upper and lower chambers
• All three associations come from observational genetic studies; no confirmed biological mechanism has been established at this specific locus
• Neither LINC02463 nor RN7SL865P has a characterized role in cardiac function in the reporting studies, making the mechanism of any effect uncertain

What the research says A cross-population GWAS meta-analysis of 252,438 AF cases and over 2 million total participants identified 525 genome-wide significant loci, including the LINC02463 region, with common variants collectively accounting for an estimated 11.2% (95% CI: 9.2-13.2%) of AF liability variance at an assumed 2% disease prevalence. In approximately 67,000 UK Biobank participants, a two-stage GWAS identified 30 loci for heart rate response to exercise and post-exercise recovery, enriched in neural development and autonomic nervous system pathways that modulate adrenergic activity PMID 29858569. A PR interval GWAS of over 92,000 European-descent individuals identified 44 genome-wide significant loci, with more than half of the index variants also showing pleiotropy with other electrophysiologic traits including heart rate, QRS interval, and AF PMID 30046080.

Reported associations

• Atrial fibrillation: Flagged in a cross-population meta-analysis of 252,438 AF cases and over 2 million total individuals; common variants genome-wide explained 11.2% (95% CI: 9.2-13.2%) of AF liability variance at an assumed 2% disease prevalence
• Heart rate response to exercise: Identified among 30 genome-wide significant loci (P <= 5 x 10-8) for change in heart rate during an exercise test in approximately 67,000 UK Biobank participants, with pathway enrichment in autonomic nervous system modulation and neural development processes PMID 29858569
• Heart rate recovery post-exercise: Identified in the same UK Biobank cohort for heart rate recovery 1 minute after exercise; 8 loci were shared across both the exercise and recovery heart rate phenotypes PMID 29858569
• PR interval: Identified in a meta-analysis of the PR interval (the electrocardiographic measure of atrial and atrioventricular conduction time) in over 92,000 European-descent individuals; genes at the identified loci were enriched in disease processes including heart block and AF PMID 30046080

Evidence quality All three associations reached genome-wide significance (P <= 5 x 10-8) in studies with large sample sizes. The AF meta-analysis included 252,438 cases across multiple ancestries, and 479 of 493 European-ancestry loci showed consistent effect estimates between discovery and replication datasets. The heart rate exercise study used a two-stage UK Biobank design with approximately 40,000 discovery and approximately 27,000 replication participants, with six to seven SNPs formally replicating across stages PMID 29858569. The PR interval study exceeded 92,000 individuals, with PR interval heritability estimated at 40-60% from family and twin data; over half of its index variants showed pleiotropy with other cardiac electrical phenotypes, reinforcing broad biological relevance at identified loci PMID 30046080. The biological mechanism at this specific locus remains unclear, as neither nearby gene has a described cardiac function in the reporting studies. All evidence is observational, and no functional validation for this locus has been reported in the provided studies.

Lifestyle considerations No lifestyle considerations on file for this variant.