Human genome-wide association studies have linked single nucleotide 
polymorphisms (SNPs) on chromosome 9p21.3 near the INK4/ARF (CDKN2a/b) locus 
with susceptibility to atherosclerotic vascular disease (ASVD). Although this 
locus encodes three well-characterized tumor suppressors, p16(INK4a), 
p15(INK4b), and ARF, the SNPs most strongly associated with ASVD are ∼120 kb 
from the nearest coding gene within a long non-coding RNA (ncRNA) known as ANRIL 
(CDKN2BAS). While individuals homozygous for the atherosclerotic risk allele 
show decreased expression of ANRIL and the coding INK4/ARF transcripts, the 
mechanism by which such distant genetic variants influence INK4/ARF expression 
is unknown. Here, using rapid amplification of cDNA ends (RACE) and analysis of 
next-generation RNA sequencing datasets, we determined the structure and 
abundance of multiple ANRIL species. Each of these species was present at very 
low copy numbers in primary and cultured cells; however, only the expression of 
ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with 
the ASVD risk alleles. Surprisingly, RACE also identified transcripts containing 
non-colinear ANRIL exonic sequences, whose expression also correlated with 
genotype and INK4/ARF expression. These non-polyadenylated RNAs resisted RNAse R 
digestion and could be PCR amplified using outward-facing primers, suggesting 
they represent circular RNA structures that could arise from by-products of mRNA 
splicing. Next-generation DNA sequencing and splice prediction algorithms 
identified polymorphisms within the ASVD risk interval that may regulate ANRIL 
splicing and circular ANRIL (cANRIL) production. These results identify novel 
circular RNA products emanating from the ANRIL locus and suggest causal variants 
at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL 
expression and/or structure.