Study finds novel genes linked to fibromuscular dysplasia using genetic meta-analysis

Recent research identified that three novel genetic variants that control gene expression in the arteries are linked to fibromuscular dysplasia (FMD)—an arterial disease that induces threatening impacts for the heart and vessels.

The research was carried out by an international group of FMD experts from the United States and Europe. The researchers affirmed the significance of a fourth genetic target pinpointed earlier to be involved with the disease. The observations are published in the Nature Communications journal.

We once thought FMD was a rare disease, but the current estimate is that it may affect more than 3% of the population. It’s vital that we continue this research to better understand what causes FMD. The disease primarily affects women in the prime of their lives, and the diagnosis often comes after a dangerous cardiovascular complication such as severe high blood pressure, a stroke, or a heart attack.”

Santhi Ganesh, MD, Study Co-Senior and Co-Corresponding Author and Associate Professor, Internal Medicine and Human Genetics, University of Michigan Medical School

Santhi Ganesh is also a cardiologist at the University of Michigan Health Frankel Cardiovascular Center.

The scientists remark that the genes pinpointed indicate that the genetic basis of FMD might contribute through altered vascular smooth muscle cell structure and function.

Particularly, the genetic observations indicated a correlation to numerous cardiovascular diseases that are mostly reported in tandem with FMD—including migraine headache, high blood pressure, intracranial aneurysm, and subarachnoid hemorrhage. A negative correlation to atherosclerotic coronary artery disease was observed. Moreover, no shared genetics were affirmed with ischemic stroke, which also generally affects individuals with FMD.

The findings provide new biologic insights into this intriguing condition and genes and pathways to study further, toward the goal of identifying therapeutic targets for FMD.”

Nabila Bouatia-Naji PhD, Study Co-Senior and Co-Corresponding Author and Director of Research, Institut National de la Santé et de la Recherche Médicale

Institut National de la Santé et de la Recherche Médicale is also called INSERM. Nabila Bouatia-Naji is also a team leader at the Paris Cardiovascular Research Center.

Ganesh and Bouatia-Naji’s group analyzed data from genome-wide association studies of more than 1,500 FMD cases. They compared them to around 7,000 control samples from participants without FMD. ATP2B1, LRP1, and LIMA1 are the three novel genes involved in FMD, and the fourth gene that was ascertained is called PHACTR1.

This is the most comprehensive genetic investigation of FMD to date, and was made possible through the collective efforts of our international research teams.”

Santhi Ganesh, MD, Study Co-Senior and Co-Corresponding Author and Associate Professor, Internal Medicine and Human Genetics, University of Michigan Medical School