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

Qian Yang, Shengyuan Yu
In: Frontiers in Neurology · 2026 · vol. 17 , pp. 1781023 · doi:10.3389/fneur.2026.1781023 · PMID:42222530 · PMC13218954 · W7161283507
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review posits that shared genetic architecture, including pleiotropy and convergent inflammatory pathways, underlies the comorbidity of endometriosis and migraine, moving beyond hormonal explanations to a novel, mechanism-based understanding.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This review synthesizes genetic epidemiology to explain the well-described comorbidity between endometriosis and migraine, focusing on shared heritability, pleiotropy, and convergence on inflammatory and pain-sensitization pathways. Drawing together evidence from GWAS, genetic correlation (via LD score regression), and Mendelian randomization, the authors report that genetic overlap exists between the two conditions and that MR does not support a direct causal relationship, with shared risk loci such as TRIM32 and SLC44A4 converging on pathways including IL-1, TNF-α, and MAPK/ERK signaling. A key limitation highlighted is that MR relies on assumptions (e.g., instrument validity and interpretation under pleiotropy), which can affect causal inference. This paper is centrally about endometriosis and migraine—reviewing shared genetic architecture (pleiotropy) and pathway convergence that links endometriosis with migraine comorbidity.

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Abstract

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.

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Condition tags

endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (73)

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