Genetic variation in patent foramen ovale: a case-control genome-wide association study
BackgroundPatent foramen ovale (PFO) is a congenital defect between the atria, resulting in abnormal hemodynamics. We conducted a genome-wide association study (GWAS) to identify common genetic variants associated with PFO.MethodsWe performed a whole genome sequencing in a discovery cohort of 3,227...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1523304/full |
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| author | Bosi Dong Yajiao Li Fandi Ai Jia Geng Ting Tang Wan Peng Yusha Tang Hui Wang Zixuan Tian Fengxiao Bu Lei Chen |
| author_facet | Bosi Dong Yajiao Li Fandi Ai Jia Geng Ting Tang Wan Peng Yusha Tang Hui Wang Zixuan Tian Fengxiao Bu Lei Chen |
| author_sort | Bosi Dong |
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| description | BackgroundPatent foramen ovale (PFO) is a congenital defect between the atria, resulting in abnormal hemodynamics. We conducted a genome-wide association study (GWAS) to identify common genetic variants associated with PFO.MethodsWe performed a whole genome sequencing in a discovery cohort of 3,227 unrelated Chinese participants screened for PFO via contrast transthoracic echocardiography (cTTE). Single-nucleotide polymorphisms (SNPs) associated with PFO were further validated by Sanger sequencing and subsequently were evaluated in a validation cohort. Expression quantitative trait loci (eQTL) analysis was conducted using the GTEx database. Single-cell sequencing analyses with pseudotime trajectory modeling were employed to evaluate their expression in human fetal hearts.ResultsThe case-control GWAS of discovery cohort ultimately included 517 cases and 517 demographically matched controls. Of the 7,040,407 variants assessed, we identified rs1227675732 (OR = 2.903; 95% CI, 1.961 to 4.297; p = 3.05 × 10−8), rs62206790 (OR = 2.780; 95% CI, 1.864 to 4.146; p = 2.02 × 10−7), rs879176184 (OR = 2.724; 95% CI, 1.822 to 4.073; p = 4.30 × 10−7) and rs13115019 (OR = 2.437; 95% CI, 1.702 to 3.488; p = 5.80 × 10−7) as high-risk variants for PFO, while rs57922961 (OR = 0.5081; 95% CI, 0.388 to 0.666; p = 6.82 × 10−7) was identified as protective variant. These variations were replicated in the validation cohort (111 cases and 152 controls). Single-cell sequencing showed that CNOT2, KCNMB4, MLLT10, IGBP1, and FRG1 were highly expressed with significant changes during heart development.ConclusionThe identification of susceptible loci for PFO might provide insights into the pathogenesis of PFO and contribute to understanding heart development.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=40590, identifier ChiCTR1900024623. |
| format | Article |
| id | doaj-art-c4df83b20ba2450ca9e50e07a857bcec |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Genetics |
| spelling | doaj-art-c4df83b20ba2450ca9e50e07a857bcec2025-01-13T06:10:58ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.15233041523304Genetic variation in patent foramen ovale: a case-control genome-wide association studyBosi Dong0Yajiao Li1Fandi Ai2Jia Geng3Ting Tang4Wan Peng5Yusha Tang6Hui Wang7Zixuan Tian8Fengxiao Bu9Lei Chen10Department of Neurology, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital of Sichuan University, Chengdu, ChinaInstitute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, ChinaInstitute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, ChinaInstitute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, ChinaInstitute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Neurology, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Neurology, West China Hospital of Sichuan University, Chengdu, ChinaInstitute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Neurology, West China Hospital of Sichuan University, Chengdu, ChinaBackgroundPatent foramen ovale (PFO) is a congenital defect between the atria, resulting in abnormal hemodynamics. We conducted a genome-wide association study (GWAS) to identify common genetic variants associated with PFO.MethodsWe performed a whole genome sequencing in a discovery cohort of 3,227 unrelated Chinese participants screened for PFO via contrast transthoracic echocardiography (cTTE). Single-nucleotide polymorphisms (SNPs) associated with PFO were further validated by Sanger sequencing and subsequently were evaluated in a validation cohort. Expression quantitative trait loci (eQTL) analysis was conducted using the GTEx database. Single-cell sequencing analyses with pseudotime trajectory modeling were employed to evaluate their expression in human fetal hearts.ResultsThe case-control GWAS of discovery cohort ultimately included 517 cases and 517 demographically matched controls. Of the 7,040,407 variants assessed, we identified rs1227675732 (OR = 2.903; 95% CI, 1.961 to 4.297; p = 3.05 × 10−8), rs62206790 (OR = 2.780; 95% CI, 1.864 to 4.146; p = 2.02 × 10−7), rs879176184 (OR = 2.724; 95% CI, 1.822 to 4.073; p = 4.30 × 10−7) and rs13115019 (OR = 2.437; 95% CI, 1.702 to 3.488; p = 5.80 × 10−7) as high-risk variants for PFO, while rs57922961 (OR = 0.5081; 95% CI, 0.388 to 0.666; p = 6.82 × 10−7) was identified as protective variant. These variations were replicated in the validation cohort (111 cases and 152 controls). Single-cell sequencing showed that CNOT2, KCNMB4, MLLT10, IGBP1, and FRG1 were highly expressed with significant changes during heart development.ConclusionThe identification of susceptible loci for PFO might provide insights into the pathogenesis of PFO and contribute to understanding heart development.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=40590, identifier ChiCTR1900024623.https://www.frontiersin.org/articles/10.3389/fgene.2024.1523304/fullpatent foramen ovalegenome-wide association studyheart developmentcommon variantssingle-cell sequencing |
| spellingShingle | Bosi Dong Yajiao Li Fandi Ai Jia Geng Ting Tang Wan Peng Yusha Tang Hui Wang Zixuan Tian Fengxiao Bu Lei Chen Genetic variation in patent foramen ovale: a case-control genome-wide association study Frontiers in Genetics patent foramen ovale genome-wide association study heart development common variants single-cell sequencing |
| title | Genetic variation in patent foramen ovale: a case-control genome-wide association study |
| title_full | Genetic variation in patent foramen ovale: a case-control genome-wide association study |
| title_fullStr | Genetic variation in patent foramen ovale: a case-control genome-wide association study |
| title_full_unstemmed | Genetic variation in patent foramen ovale: a case-control genome-wide association study |
| title_short | Genetic variation in patent foramen ovale: a case-control genome-wide association study |
| title_sort | genetic variation in patent foramen ovale a case control genome wide association study |
| topic | patent foramen ovale genome-wide association study heart development common variants single-cell sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1523304/full |
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