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 confirmed PHACTR1 and identified three new loci (LRP1, ATP2B1, and LIMA1) 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.

中文翻译：

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纤维肌肉发育不良的遗传关联研究确定了新的风险基因座，并与更常见的血管疾病共享了遗传基础

纤维肌发育不良（FMD）是一种临床上由高血压和中风引起的动脉病，主要发生在中年早期的女性中。我们报告的结果包括1962年的FMD病例和7100个对照的FMD的首次全基因组关联荟萃分析。我们确认了PHACTR1，并确定了与FMD相关的三个新基因座（LRP1，ATP2B1和LIMA1）。动脉中的转录组范围的关联分析确定了另外一个基因座（SLC24A3）。FMD相关变体位于血管平滑肌细胞和成纤维细胞中活跃的动脉特异性增强子中。靶基因广泛参与与肌动蛋白细胞骨架和细胞内钙稳态有关的机制，这些机制对血管收缩至关重要。跨性格连锁不平衡分析确定与血压呈正相关，