**7. Future Research Directions and Clinical Perspectives**

In view of the relatively modest association of rs9349379[A] with FMD [46], compatible with polygenic inheritance, and the poor yield of screening for mutations in genes involved in CTD [36–38], genetic testing has currently no place in the diagnosis and management of the disease outside a research context [1]. Still, progressive dissection of the genetic basis of FMD paves the way for a better understanding of the disease, which may hopefully lead to identification of accurate prognostic biomarkers and novel preventive and therapeutic options.

The association of FMD with the intronic variant in *PHACTR1* needs to be replicated in large and independent cohorts of patients with more balanced representation of renal and cervico-cephalic FMD, and tested in related conditions, such as SCAD. Whether this association is restricted to multifocal FMD or is also present in patients with focal FMD, and whether it is modulated by gender, ethnic background, tobacco exposure and/or other environmental factors remains to be demonstrated. More studies are also needed to better understand the dichotomic effect of the *PHACTR1* locus on FMD and related vascular diseases on one side, and on atherosclerotic coronary artery disease on the other side. Larger cohorts obtained through international collaborations should also facilitate identification of other susceptibility loci associated with FMD. Unveiling of genetic factors underlying FMD and their interactions with environmental factors may allow (i) to propose a more accurate classification of the disease; (ii) to identify subsets of patients with FMD associated with a higher risk of progression/complications; and (iii) to ascertain or not the dysplastic nature of arterial

aneurysms and/or dissections occurring in patients without typical string-of-beads or focal FMD stenosis. Such advances in our understanding of the genetic basis of FMD are critically dependent on ongoing efforts to develop large scale registries including patients with FMD and related diseases, such as the US and European/International registries [3,39].

**Conflicts of Interest:** The authors declare no conflict of interest.
