Advancements in the Genetics of Spontaneous Coronary Artery Dissection

Figures

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  Fig. 1. Genetic, biologic, and clinical associations to SCAD. SCAD is linked to several other conditions and may be indicative of an underlying systemic arteriopathy such as fibromuscular dysplasia (FMD, depicted as renal artery involvement in the top circle), with risk factors involving sex-specific biologic associations and hormonal milieu including pregnancy (right upper circle). SCAD has a complex genetic architecture that is also associated with FMD and migraine headache (right lower circle), with additional risks conferred by hypertension (lower circle) or other triggers. Monogenic connective tissue disorders have been implicated in a subset of individuals with SCAD (left lower circle), and genetic discovery studies thus far highlight biologic mechanisms involving matricellular alterations involving the arterial vascular smooth muscle (left upper circle)

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  Fig. 2. Emerging genetic architecture of SCAD. The genetic architecture of SCAD encompasses a spectrum of effect sizes and allele frequencies. Rare pathogenic variants in genes associated with Mendelian disorders confer large effect sizes. Low-frequency variants in some of the same genes and extracellular matrix genes would not meet clinical standards for pathogenicity for monogenic disease, but they have been demonstrated in aggregate to contribute to the phenotypic expression of SCAD. Common variants with lower effect sizes have also been found through association studies and represent risk susceptibility loci for SCAD. Effect size here is estimated through an inverse relationship with calculated or expected odds ratios. (Figure adapted from: Nature. 2009;461(7265):747–753, with permission of Springer Nature) [64]