Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association study
Migraine is a common neurological disorder that affects more than one billion people worldwide. Recent genome-wide association studies have identified 123 genetic loci associated with migraine risk. However, the biological mechanisms underlying migraine and its relationships with other complex disea...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1301208/full |
| _version_ | 1797322530750464000 |
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| author | Di Ouyang Di Ouyang Chunying Huang Huihua Liu Weiming Xie Chengsheng Chen Ben Su Lizhong Guo |
| author_facet | Di Ouyang Di Ouyang Chunying Huang Huihua Liu Weiming Xie Chengsheng Chen Ben Su Lizhong Guo |
| author_sort | Di Ouyang |
| collection | DOAJ |
| description | Migraine is a common neurological disorder that affects more than one billion people worldwide. Recent genome-wide association studies have identified 123 genetic loci associated with migraine risk. However, the biological mechanisms underlying migraine and its relationships with other complex diseases remain unclear. We performed a phenome-wide association study (PheWAS) using UK Biobank data to investigate associations between migraine and 416 phenotypes. Mendelian randomization was employed using the IVW method. For loci associated with multiple diseases, pleiotropy was tested using MR-Egger. Single-cell RNA sequencing data was analyzed to profile the expression of 73 migraine susceptibility genes across brain cell types. qPCR was used to validate the expression of selected genes in microglia. PheWAS identified 15 disorders significantly associated with migraine, with one association detecting potential pleiotropy. Single-cell analysis revealed elevated expression of seven susceptibility genes (including ZEB2, RUNX1, SLC24A3, ANKDD1B, etc.) in brain glial cells. And qPCR confirmed the upregulation of these genes in LPS-treated microglia. This multimodal analysis provides novel insights into the link between migraine and other diseases. The single-cell profiling suggests the involvement of specific brain cells and molecular pathways. Validation of gene expression in microglia supports their potential role in migraine pathology. Overall, this study uncovers pleiotropic relationships and the biological underpinnings of migraine susceptibility. |
| first_indexed | 2024-03-08T05:15:38Z |
| format | Article |
| id | doaj.art-f50416d995cd4e768a82b126c276f55e |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-08T05:15:38Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-f50416d995cd4e768a82b126c276f55e2024-02-07T04:33:13ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-02-011510.3389/fneur.2024.13012081301208Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association studyDi Ouyang0Di Ouyang1Chunying Huang2Huihua Liu3Weiming Xie4Chengsheng Chen5Ben Su6Lizhong Guo7Nanjing University of Chinese Medicine, Nanjing, ChinaTraditional Chinese Medicine Hospital of Yulin, Yulin, ChinaTraditional Chinese Medicine Hospital of Yulin, Yulin, ChinaTraditional Chinese Medicine Hospital of Yulin, Yulin, ChinaGuangxi Medical University, Nanning, ChinaHubei University of Chinese Medicine, Wuhan, ChinaShanghai University of Traditional Chinese Medicine, Shanghai, ChinaNanjing University of Chinese Medicine, Nanjing, ChinaMigraine is a common neurological disorder that affects more than one billion people worldwide. Recent genome-wide association studies have identified 123 genetic loci associated with migraine risk. However, the biological mechanisms underlying migraine and its relationships with other complex diseases remain unclear. We performed a phenome-wide association study (PheWAS) using UK Biobank data to investigate associations between migraine and 416 phenotypes. Mendelian randomization was employed using the IVW method. For loci associated with multiple diseases, pleiotropy was tested using MR-Egger. Single-cell RNA sequencing data was analyzed to profile the expression of 73 migraine susceptibility genes across brain cell types. qPCR was used to validate the expression of selected genes in microglia. PheWAS identified 15 disorders significantly associated with migraine, with one association detecting potential pleiotropy. Single-cell analysis revealed elevated expression of seven susceptibility genes (including ZEB2, RUNX1, SLC24A3, ANKDD1B, etc.) in brain glial cells. And qPCR confirmed the upregulation of these genes in LPS-treated microglia. This multimodal analysis provides novel insights into the link between migraine and other diseases. The single-cell profiling suggests the involvement of specific brain cells and molecular pathways. Validation of gene expression in microglia supports their potential role in migraine pathology. Overall, this study uncovers pleiotropic relationships and the biological underpinnings of migraine susceptibility.https://www.frontiersin.org/articles/10.3389/fneur.2024.1301208/fullmigrainemicrogliaphenome-wide association studysingle-cell RNA sequencinggenetic association studysusceptibility gen |
| spellingShingle | Di Ouyang Di Ouyang Chunying Huang Huihua Liu Weiming Xie Chengsheng Chen Ben Su Lizhong Guo Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association study Frontiers in Neurology migraine microglia phenome-wide association study single-cell RNA sequencing genetic association study susceptibility gen |
| title | Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association study |
| title_full | Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association study |
| title_fullStr | Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association study |
| title_full_unstemmed | Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association study |
| title_short | Comprehensive analysis of genetic associations and single-cell expression profiles reveals potential links between migraine and multiple diseases: a phenome-wide association study |
| title_sort | comprehensive analysis of genetic associations and single cell expression profiles reveals potential links between migraine and multiple diseases a phenome wide association study |
| topic | migraine microglia phenome-wide association study single-cell RNA sequencing genetic association study susceptibility gen |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1301208/full |
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