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Meta-Analysis
. 2020 Feb 29;11(3):268.
doi: 10.3390/genes11030268.

Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity

Emmanuel O Adewuyi  1 , Yadav Sapkota  2 , International Endogene Consortium Iec, andMe Research Team  3 , International Headache Genetics Consortium Ihgc, Asa Auta  4 , Kosuke Yoshihara  5 , Mette Nyegaard  6   7 , Lyn R Griffiths  1 , Grant W Montgomery  8 , Daniel I Chasman  9 , Dale R Nyholt  1
Affiliations
Meta-Analysis

Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity

Emmanuel O Adewuyi et al. Genes (Basel). .

Abstract

Observational epidemiological studies indicate that endometriosis and migraine co-occur within individuals more than expected by chance. However, the aetiology and biological mechanisms underlying their comorbidity remain unknown. Here we examined the relationship between endometriosis and migraine using genome-wide association study (GWAS) data. Single nucleotide polymorphism (SNP) effect concordance analysis found a significant concordance of SNP risk effects across endometriosis and migraine GWAS. Linkage disequilibrium score regression analysis found a positive and highly significant genetic correlation (rG = 0.38, P = 2.30 × 10-25) between endometriosis and migraine. A meta-analysis of endometriosis and migraine GWAS data did not reveal novel genome-wide significant SNPs, and Mendelian randomisation analysis found no evidence for a causal relationship between the two traits. However, gene-based analyses identified two novel loci for migraine. Also, we found significant enrichment of genes nominally associated (Pgene < 0.05) with both traits (Pbinomial-test = 9.83 × 10-6). Combining gene-based p-values across endometriosis and migraine, three genes, two (TRIM32 and SLC35G6) of which are at novel loci, were genome-wide significant. Genes having Pgene < 0.1 for both endometriosis and migraine (Pbinomial-test = 1.85 ×10-°3) were significantly enriched for biological pathways, including interleukin-1 receptor binding, focal adhesion-PI3K-Akt-mTOR-signaling, MAPK and TNF-α signalling. Our findings further confirm the comorbidity of endometriosis and migraine and indicate a non-causal relationship between the two traits, with shared genetically-controlled biological mechanisms underlying the co-occurrence of the two disorders.

Keywords: GWAS; Mendelian randomisation; causality; comorbidity; endometriosis; gene-based association study; genetic overlap; migraine; molecular genetics; pathway enrichment study.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clustered biological themes for overlapping endometriosis–migraine genes.
See this image and copyright information in PMC

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