Genetic Overlap of Thoracic Aortic Aneurysms and Intracranial Aneurysms

Thoracic aortic aneurysms (TAAs) and intracranial aneurysms (ICAs) share overlapping genetic and pathophysiological mechanisms, yet the genetic interplay between these conditions remains insufficiently explored. This study aimed to identify common genetic factors underlying TAA and ICA.

A comprehensive review of genome-wide association studies (GWASs) and retrospective clinical studies was conducted using PubMed, Orbis, and Web of Science. Articles addressing the genetic etiologies of TAA and ICA were analyzed. Separate lists of causative genes were compiled, and commonalities were identified. A Venn diagram was constructed to illustrate genetic overlap and shared physiological pathways.

We identified 24 overlapping genes associated with TAA and ICA, including LTBP2, TGFB2, TGFB3, TGFBR1, TGFBR2, SMAD2, SMAD3, COL1A2, COL3A1, COL4A1, COL5A1, COL5A2, FBN1, FBN2, ELN, LOX ACTA2, MYH11, MYLK, ABCC6, NOTCH1, MED12, PKD1, and PKD2. These genes are involved in pathways related to connective tissue biology, contractile elements, extracellular matrix components, and transforming growth factor-β signaling. While vascular endothelium and cell cycle pathways were unique to ICA, TAA pathways predominantly involved extracellular matrix remodeling.

This study highlights the significant genetic overlap between TAA and ICA, shedding light on shared molecular mechanisms. These findings underscore the importance of interdisciplinary awareness: neurologists, neurosurgeons, and neurointerventional radiologists should monitor ICA patients for potential TAA, while cardiologists, cardiac surgeons, vascular surgeons, and vascular interventionalists should consider ICA risks in TAA patients. Further research into these genetic pathways could enhance the understanding and management of both conditions.