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Polygenic Risk in Families With Spontaneous SCAD
Quick Takes
- In this genetic association study, a polygenic risk score for spontaneous coronary artery dissection (SCAD) was associated with higher odds of SCAD in both familial and sporadic cases.
- Common genetic variants may explain familial clustering in SCAD.
- In this study, rare variants in genes associated with connective tissue diseases were not identified in familial cases of SCAD.
Study Questions:
What is the contribution of rare and common genetic variants to spontaneous coronary artery dissection (SCAD)?
Methods:
By using a polygenic risk score (PRS), familial cases of SCAD were compared with sporadic cases of SCAD and healthy controls enrolled from 2017 to 2021. The PRS consisted of seven single-nucleotide variants. Additionally, genetic variants associated with connective tissues disorders were also assessed.
Results:
A total of 188 individuals with SCAD were included (94% female; 27 with familial SCAD; 173 with sporadic SCAD) and 1,127 healthy controls. When compared with controls, the odds of having SCAD were significantly associated with the SCAD PRS (affected family member: odds ratio [OR], 2.14; 95% confidence interval [CI], 1.78-2.50 and sporadic cases: OR, 1.63; 95% CI, 1.37-1.89). Unaffected family members did not have elevated PRS. Individuals with familial SCAD did not share any rare deleterious variants in connective tissue disease–associated genes.
Conclusions:
The authors conclude that common polygenic variants contribute to the familial clustering of SCAD cases. Rare variants in genes previously implicated in SCAD were not identified in the families in this study.
Perspective:
SCAD predominantly affects women and the pathogenesis remains poorly understood. Although only a small number of patients with SCAD have genetic variants associated with connective tissue disorders, familial clustering of SCAD cases is well recognized. This study compared families with SCAD, sporadic cases of SCAD, and healthy controls to demonstrate that a SCAD PRS was associated with familial cases of SCAD. Similarly, the genetic contribution to several adult-onset diseases is increasingly recognized and understood. For instance, elevated polygenic risk has been reported in familial disease versus controls for complex diseases such as melanoma, bipolar disorder, migraine, and epilepsy. Since SCAD is life-threatening and can occur unexpectedly, the development of genetic screening tools for individuals at risk is of paramount importance, and this study adds to our understanding and appreciation of the genetic contribution to SCAD.
Clinical Topics: Prevention
Keywords: Dissection, Genetic Variation, Heart Disease Risk Factors
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