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Fibromuscular dysplasia (FMD) is an arteriopathy that presents clinically by hypertension and stroke, mostly in early middle-aged women. We report results from the first genome-wide association meta-analysis of FMD including 1962 FMD cases and 7100 controls. We confirmedPHACTR1and identified three new loci (LRP1, ATP2B1, andLIMA1)associated with FMD. Transcriptome-wide association analysis in arteries identified one additional locus (SLC24A3). FMD associated variants were located in arterial-specific enhancers active in vascular smooth muscle cells and fibroblasts. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. Cross-trait linkage disequilibrium analyses identified positive genetic correlations with blood pressure, migraine and intracranial aneurysm, and an inverse correlation with coronary artery disease, independent from the genetics of blood pressure.

Cryptoprocta ferox, or fosa, is the largest living endemic carnivoran of Madagascar, with presumably high dispersal capacity, and for which no broad scale phylogeographic study has been conducted to date. This species is considered “Vulnerable” by the IUCN and the subject of a captive breeding program; approximately 113 individuals are held in 57 zoos. The aim of this study was to examine the genetic structure and polymorphism within both captive and wild populations, to determine possible lineage variation, and to make recommendations for the captive breeding program. For this purpose, we analyzed three mitochondrial (Cytochrome b, ND2, Control Region) and one nuclear (Beta-fibrinogen intron 7) markers. The results showed an overall low level of genetic polymorphism, likely related to its dispersal capacity, and some genetic structure possibly associated with geographical barriers, such as large rivers. The genetic diversity of the captive population was greater than that of wild individuals included herein, suggesting that the captive population encompasses a considerable proportion of the genetic diversity of the species. This genetic variability is presumably the consequence of frequent imports of wild animals into zoos from different areas of Madagascar, and subsequent exchanges between zoos. Based on the low overall genetic polymorphism of the species and the absence of deeply divergent lineages, we recommend the continued mixing of captive animals. Our results may help the management of the fosa in the wild and in captivity, which is crucial for a species that faces many threats in the wild, in particular habitat degradation and hunting pressure. In any case, enhanced protection of the species and its forested habitat is urgently needed.

The Malagasy carnivorans (Eupleridae) comprise seven genera and up to ten species, depending on the authority, and, within the past decades, two new taxa have been described. The family is divided into two subfamilies, the Galidiinae, mongoose-like animals, and the Euplerinae, with diverse body forms. To verify the taxonomic status of Galidiinae species, including recently described taxa, as well as some recognized subspecies, we studied intrageneric genetic variation and structure, using both mitochondrial and nuclear markers. Our results suggest the recognition of four species in the Galidiinae, rendering each genus monospecific. We propose to recognize three subspecies in Galidia elegans (G. e. dambrensis, G. e. elegans, and G. e. occidentalis), two subspecies in Mungotictis decemlineata (M. d. decemlineata and M. d. lineata), and two subspecies in Galidictis fasciata (G. f. fasciata and G. f. grandidieri, the latter was recently described as a distinct species). Our results indicate also that Salanoia durrelli should be treated as a junior synonym of Salanoia concolor. Low levels of intraspecific divergence revealed some geographical structure for the Galidiinae taxa, suggesting that environmental barriers have isolated certain populations in recent geological time. All taxa, whether at the species or subspecies level, need urgent conservation attention, particularly those with limited geographical distributions, as all are threatened by forest habitat degradation.

Background Fibromuscular Dysplasia (FMD) and Spontaneous Coronary Artery Dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. Objectives We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in FMD and SCAD. Methods We analyzed 29 exomes that included familial and sporadic FMD. Follow-up was conducted by targeted or Sanger sequencing (1,071 FMD and 365 SCAD patients) or lookups in exome (264 FMD) or genome sequences (488 SCAD), all independent and unrelated. We used TRAPD burden test to test for enrichment in patients compared to gnomAD controls. The biological effects of variants on receptor signaling and protein expression were characterized using transient overexpression in human cells. Results We identified one rare loss-of-function variant (LoF) (MAFgnomAD = 0.000075) shared by two FMD sisters in the prostaglandin I2 receptor (hIP) gene (PTGIR), a key player in vascular remodeling. Follow-up in > 1,300 FMD patients revealed four additional LoF allele carriers and a putative enrichment in FMD (PTRAPD = 8 × 10-4), in addition to several rare missense variants. We confirmed the LoFs (Q163X and P17RfsX6) and one missense (L67P) to severely impair hIP function in vitro. Genetic analyses of PTGIR in SCAD revealed one patient who carries Q163X, one with L67P and one carrying a rare splicing mutation (c.768 + 1C > G), but not a significant enrichment (PTRAPD = 0.12) in SCAD. Conclusions Our study shows that rare genetic mutations in PTGIR are enriched among FMD patients and found in SCAD patients, suggesting a role for prostacyclin signaling in non-atherosclerotic stenosis and dissection.