Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity
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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | http://hdl.handle.net/20.500.11937/97784 |
| _version_ | 1848766315253202944 |
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| author | Adewuyi, Emmanuel Sapkota, Y. Auta, A. Yoshihara, K. Nyegaard, M. Griffiths, L.R. Montgomery, G.W. Chasman, D.I. Nyholt, D.R. |
| author_facet | Adewuyi, Emmanuel Sapkota, Y. Auta, A. Yoshihara, K. Nyegaard, M. Griffiths, L.R. Montgomery, G.W. Chasman, D.I. Nyholt, D.R. |
| author_sort | Adewuyi, Emmanuel |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T11:49:11Z |
| format | Journal Article |
| id | curtin-20.500.11937-97784 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:49:11Z |
| publishDate | 2020 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-977842025-05-22T14:53:02Z Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity Adewuyi, Emmanuel Sapkota, Y. Auta, A. Yoshihara, K. Nyegaard, M. Griffiths, L.R. Montgomery, G.W. Chasman, D.I. Nyholt, D.R. GWAS Mendelian randomisation causality comorbidity endometriosis gene-based association study genetic overlap migraine molecular genetics pathway enrichment study Adult Aged Comorbidity Endometriosis Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Linkage Disequilibrium Mendelian Randomization Analysis Middle Aged Migraine Disorders Phenotype Phosphatidylinositol 3-Kinases Polymorphism, Single Nucleotide Risk Factors Humans Endometriosis Genetic Predisposition to Disease Risk Factors Comorbidity Linkage Disequilibrium Phenotype Polymorphism, Single Nucleotide Adult Aged Middle Aged Female Migraine Disorders Genome-Wide Association Study Mendelian Randomization Analysis Phosphatidylinositol 3-Kinases 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. 2020 Journal Article http://hdl.handle.net/20.500.11937/97784 10.3390/genes11030268 eng unknown |
| spellingShingle | GWAS Mendelian randomisation causality comorbidity endometriosis gene-based association study genetic overlap migraine molecular genetics pathway enrichment study Adult Aged Comorbidity Endometriosis Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Linkage Disequilibrium Mendelian Randomization Analysis Middle Aged Migraine Disorders Phenotype Phosphatidylinositol 3-Kinases Polymorphism, Single Nucleotide Risk Factors Humans Endometriosis Genetic Predisposition to Disease Risk Factors Comorbidity Linkage Disequilibrium Phenotype Polymorphism, Single Nucleotide Adult Aged Middle Aged Female Migraine Disorders Genome-Wide Association Study Mendelian Randomization Analysis Phosphatidylinositol 3-Kinases Adewuyi, Emmanuel Sapkota, Y. Auta, A. Yoshihara, K. Nyegaard, M. Griffiths, L.R. Montgomery, G.W. Chasman, D.I. Nyholt, D.R. Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity |
| title | Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity |
| title_full | Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity |
| title_fullStr | Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity |
| title_full_unstemmed | Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity |
| title_short | Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity |
| title_sort | shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity |
| topic | GWAS Mendelian randomisation causality comorbidity endometriosis gene-based association study genetic overlap migraine molecular genetics pathway enrichment study Adult Aged Comorbidity Endometriosis Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Linkage Disequilibrium Mendelian Randomization Analysis Middle Aged Migraine Disorders Phenotype Phosphatidylinositol 3-Kinases Polymorphism, Single Nucleotide Risk Factors Humans Endometriosis Genetic Predisposition to Disease Risk Factors Comorbidity Linkage Disequilibrium Phenotype Polymorphism, Single Nucleotide Adult Aged Middle Aged Female Migraine Disorders Genome-Wide Association Study Mendelian Randomization Analysis Phosphatidylinositol 3-Kinases |
| url | http://hdl.handle.net/20.500.11937/97784 |