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Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity.

Published on Feb 29, 2020in Genes3.331
· DOI :10.3390/GENES11030268
Emmanuel Olorunleke Adewuyi9
Estimated H-index: 9
(QUT: Queensland University of Technology),
Yadav Sapkota14
Estimated H-index: 14
(St. Jude Children's Research Hospital)
+ 6 AuthorsGrant W. Montgomery123
Estimated H-index: 123
(UQ: University of Queensland)
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.
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#1Lorraine Maitrot-Mantelet (Paris V: Paris Descartes University)H-Index: 1
#1Lorraine Maitrot-Mantelet (Paris V: Paris Descartes University)H-Index: 2
Last. Geneviève Plu-Bureau (Paris V: Paris Descartes University)H-Index: 2
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BackgroundStudies have shown a significant association between migraine and endometriosis, but no study has explored the relationship between migraine and endometriosis phenotypes: Superficial peri...
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Abstract Purpose Migraines are the third most prevalent disorder, and seventh-highest specific cause of disability worldwide. Migraines have a multitude of underlying aetiologies; the pathology may come as a result of hormonal treatment or as a sole symptom during menstrual cycle or pregnancy, with variable intensity and duration. In addition, clinicians should be fully aware of the potential complications and well-versed in management options. Methods A systematic review of the incidence, sympt...
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Pathway enrichment analysis helps researchers gain mechanistic insight into gene lists generated from genome-scale (omics) experiments. This method identifies biological pathways that are enriched in a gene list more than would be expected by chance. We explain the procedures of pathway enrichment analysis and present a practical step-by-step guide to help interpret gene lists resulting from RNA-seq and genome-sequencing experiments. The protocol comprises three major steps: definition of a gene...
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Introduction:Available data suggest that there is an association between endometriosis and a group of disorders including autonomic nervous system irregularities. A deeper understanding of relation...
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Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based her...
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