Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications
Post-traumatic stress disorder (PTSD) is a psychiatric disorder that frequently co-occurs with pain disorders including migraine. There are proposed biological, genetic and environmental factors associated with both PTSD and migraine suggesting shared etiology. Genome-Wide Association Studies (GWAS)...
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Elsevier
2025-01-01
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| Series: | Neurobiology of Stress |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289524000997 |
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| author | Charlotte K. Bainomugisa Dagmar Bruenig Heidi G. Sutherland Lyn R. Griffiths Dale R. Nyholt Divya Mehta |
| author_facet | Charlotte K. Bainomugisa Dagmar Bruenig Heidi G. Sutherland Lyn R. Griffiths Dale R. Nyholt Divya Mehta |
| author_sort | Charlotte K. Bainomugisa |
| collection | DOAJ |
| description | Post-traumatic stress disorder (PTSD) is a psychiatric disorder that frequently co-occurs with pain disorders including migraine. There are proposed biological, genetic and environmental factors associated with both PTSD and migraine suggesting shared etiology. Genome-Wide Association Studies (GWAS) have been used to identify genomic risk loci associated with various disorders and to investigate genetic overlap between traits. There is a significant genetic correlation between PTSD and migraine with no evidence of a causal relationship that could be attributed to pleiotropy. Cross-disorder genetic analyses were applied to investigate the genetic overlap and causal associations using GWAS summary statistics of PTSD (n = 214408), migraine (n = 873341) and 23 medication use traits (n = 78808–305913) including anti-depressants, anti-migraine preparations and beta-blocking agents.Across the entire genome, anti-thrombotic agents had a significant and negative genetic correlation with PTSD (rG = −0.2, PFDR = 0.032) and a positive genetic correlation with migraine (rG = 0.26, PFDR = 2.23 x 10−8). PTSD showed significant genetic correlation with 11 other medication use traits including beta blocking agents (rG = −0.11, PFDR = 0.034). Of the 2495 genomic regions tested, PTSD showed significant local genetic correlation with 12 medication use traits at 43 loci; while migraine showed significant genetic correlation with only anti-inflammatory agents and anti-rheumatic products at locus 12:57522282–57607142 (DAB1) (P < 2 x 10−5). The genetic liability to PTSD had a causal effect on increased risk of using pain medication such as opioids (βivw = 0.59, P = 5.21 x 10−5) while the genetic liability to migraine had a causal effect on the increased risk of using anti-thrombotic agents (βivw = 0.59, P = 1.69 x 10−7). The genes in the genomic regions shared between PTSD and medication use traits were enriched in neural-related pathways such as neuron development, neurogenesis and protein kinase activity. These results provide further insight into the genetically controlled biological and environmental factors underlying the shared etiology between PTSD and migraine. The identified biomarkers can be used as a basis for investigation as potential drug targets for both disorders. These findings are significant for drug re-purposing and treatment of PTSD and migraine using monotherapy. |
| format | Article |
| id | doaj-art-dcd1cc9a11504cd59e7f6144a46a8e81 |
| institution | Kabale University |
| issn | 2352-2895 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Neurobiology of Stress |
| spelling | doaj-art-dcd1cc9a11504cd59e7f6144a46a8e812025-01-19T06:26:09ZengElsevierNeurobiology of Stress2352-28952025-01-0134100703Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medicationsCharlotte K. Bainomugisa0Dagmar Bruenig1Heidi G. Sutherland2Lyn R. Griffiths3Dale R. Nyholt4Divya Mehta5Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia; Centre for Data Science, Queensland University of Technology, Brisbane, Queensland, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; Corresponding author. Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia.Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia; Centre for Data Science, Queensland University of Technology, Brisbane, Queensland, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, AustraliaCentre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, AustraliaCentre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, AustraliaCentre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia; Centre for Data Science, Queensland University of Technology, Brisbane, Queensland, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, AustraliaCentre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia; Centre for Data Science, Queensland University of Technology, Brisbane, Queensland, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; Corresponding author. Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia.Post-traumatic stress disorder (PTSD) is a psychiatric disorder that frequently co-occurs with pain disorders including migraine. There are proposed biological, genetic and environmental factors associated with both PTSD and migraine suggesting shared etiology. Genome-Wide Association Studies (GWAS) have been used to identify genomic risk loci associated with various disorders and to investigate genetic overlap between traits. There is a significant genetic correlation between PTSD and migraine with no evidence of a causal relationship that could be attributed to pleiotropy. Cross-disorder genetic analyses were applied to investigate the genetic overlap and causal associations using GWAS summary statistics of PTSD (n = 214408), migraine (n = 873341) and 23 medication use traits (n = 78808–305913) including anti-depressants, anti-migraine preparations and beta-blocking agents.Across the entire genome, anti-thrombotic agents had a significant and negative genetic correlation with PTSD (rG = −0.2, PFDR = 0.032) and a positive genetic correlation with migraine (rG = 0.26, PFDR = 2.23 x 10−8). PTSD showed significant genetic correlation with 11 other medication use traits including beta blocking agents (rG = −0.11, PFDR = 0.034). Of the 2495 genomic regions tested, PTSD showed significant local genetic correlation with 12 medication use traits at 43 loci; while migraine showed significant genetic correlation with only anti-inflammatory agents and anti-rheumatic products at locus 12:57522282–57607142 (DAB1) (P < 2 x 10−5). The genetic liability to PTSD had a causal effect on increased risk of using pain medication such as opioids (βivw = 0.59, P = 5.21 x 10−5) while the genetic liability to migraine had a causal effect on the increased risk of using anti-thrombotic agents (βivw = 0.59, P = 1.69 x 10−7). The genes in the genomic regions shared between PTSD and medication use traits were enriched in neural-related pathways such as neuron development, neurogenesis and protein kinase activity. These results provide further insight into the genetically controlled biological and environmental factors underlying the shared etiology between PTSD and migraine. The identified biomarkers can be used as a basis for investigation as potential drug targets for both disorders. These findings are significant for drug re-purposing and treatment of PTSD and migraine using monotherapy.http://www.sciencedirect.com/science/article/pii/S2352289524000997PTSDMigraineMedicationGWASLociGenes |
| spellingShingle | Charlotte K. Bainomugisa Dagmar Bruenig Heidi G. Sutherland Lyn R. Griffiths Dale R. Nyholt Divya Mehta Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications Neurobiology of Stress PTSD Migraine Medication GWAS Loci Genes |
| title | Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications |
| title_full | Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications |
| title_fullStr | Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications |
| title_full_unstemmed | Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications |
| title_short | Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications |
| title_sort | shared genetic risk and causal associations between post traumatic stress disorder and migraine with antithrombotic agents and other medications |
| topic | PTSD Migraine Medication GWAS Loci Genes |
| url | http://www.sciencedirect.com/science/article/pii/S2352289524000997 |
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