A review on shared genetic architecture of endometriosis and migraine: from pleiotropy to convergent inflammatory pathways.

The comorbidity between endometriosis and migraine has long been recognized clinically, yet a unifying pathophysiological explanation has remained elusive. Traditional models, centered on hormonal fluctuations or secondary inflammation are lacking to explain the fundamental predisposition underlying their co-occurrence. This review synthesizes the evidence from genetic epidemiology that is reshaping this narrative, positing that shared molecular genetic mechanisms provide the missing link. This review paper aims to present a review of the current literature surrounding genetic overlap between EM and migraine. Critically, Mendelian Randomization analyses refute a causal relationship, instead pointing to pleiotropy as the core principle. We delve into the specific shared risk loci, such as TRIM32 and SLC44A4, and demonstrate how they converge on dysregulated biological pathways, notably IL-1, TNF-α, and MAPK/ERK signaling that drive both peripheral inflammation in endometriosis and neuroinflammation in migraine. Central sensitization emerges as a critical amplifier, functionally coupling the two conditions and exacerbating chronic pain. By integrating these findings, we propose a novel model where endometriosis and migraine are parallel manifestations of a shared genetic architecture. Finally, we discuss the translational implications of this paradigm, including the potential for genetic stratification of high-risk patients and the repurposing of therapeutics targeting these shared inflammatory pathways. This genetic reframing may move the field beyond symptomatic management toward a future of mechanism-based, personalized medicine for this underserved patient population.