Background 
It is widely accepted that genetic factors may underly the pathopbiology of atherosclerosis. Here we report the findings of genetic analysis in a kindred with an autosomal dominant trait for premature MI and atherosclerosis and explored the association of a common genetic variant with the risk on ischemic heart disease in a population-based study 
Methods 
We applied next generation sequencing to elucidate the molecular defect  in a small pedigree with premature atherosclerosis. To evaluate the relevance of SUSD2 on a broader scale we assessed whether a common variant, rs8141797 (p.Asn466Ser), was associated with ischemic heart disease.
Results
 We identified a novel nonsense mutation in SUSD2 (c.G583T; p.Glu195Ter) which co-segregates with the disease phenotype in the pedigree. SUSD2 was expressed in aortic specimen. In the prospective Copenhagen General Population Study and the Copenhagen City Heart Study, homozygosity for the rare allele of rs8141797 was associated with  lower plasma LDL-C levels  (P<0.05 and decreased risk for ischemic heart disease (P for trend P=0.002) which was confirmed in a meta-analysis . 
Conclusions
A nonsense mutation in SUSD2 was identified in a small pedigree with premature MI and atherosclerosis .  The association of rs8141797 with decreased ischemic heart disease and lower plasma LDL-C lend further support for a role of SUSD2 in atherosclerosis.

07 - A COMMON AND A RARE TRUNCATING VARIANT IN SUSD2 AND RISK OF ISCHEMIC HEART DISEASE