The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study
Abstract Background This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-02074-1 |
| _version_ | 1797276027181858816 |
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| author | Pei Qin Tianhang Qin Lei Liang Xinying Li Bin Jiang Xiaojie Wang Jianping Ma Fulan Hu Ming Zhang Dongsheng Hu |
| author_facet | Pei Qin Tianhang Qin Lei Liang Xinying Li Bin Jiang Xiaojie Wang Jianping Ma Fulan Hu Ming Zhang Dongsheng Hu |
| author_sort | Pei Qin |
| collection | DOAJ |
| description | Abstract Background This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). Methods Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. Results Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (β= − 0.060, 95% CI − 0.044 to − 0.076; P = 2.416e−14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (β= − 0.021, 95% CI − 0.003 to − 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. Conclusions Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice. |
| first_indexed | 2024-03-07T15:22:26Z |
| format | Article |
| id | doaj.art-f57a4fb3441145bfa27deebf6fc89572 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-07T15:22:26Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-f57a4fb3441145bfa27deebf6fc895722024-03-05T17:36:34ZengBMCCardiovascular Diabetology1475-28402024-01-0123111410.1186/s12933-023-02074-1The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization studyPei Qin0Tianhang Qin1Lei Liang2Xinying Li3Bin Jiang4Xiaojie Wang5Jianping Ma6Fulan Hu7Ming Zhang8Dongsheng Hu9Department of General Practice, The Affiliated Luohu Hospital of Shenzhen UniversityInstitute of Software Chinese Academy of SciencesDepartment of Gynecology and Obstetrics, Shenzhen Qianhai Shekou Free Trade Zone HospitalSchool of Public Health, Shantou UniversityDepartment of Neurology, Shenzhen Qianhai Shekou Free Trade Zone HospitalDepartment of Neurology, Shenzhen Qianhai Shekou Free Trade Zone HospitalDepartment of Neurology, Shenzhen Qianhai Shekou Free Trade Zone HospitalSchool of Public Health, Shenzhen University Health Science CenterSchool of Public Health, Shenzhen University Health Science CenterDepartment of General Practice, The Affiliated Luohu Hospital of Shenzhen UniversityAbstract Background This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). Methods Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. Results Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (β= − 0.060, 95% CI − 0.044 to − 0.076; P = 2.416e−14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (β= − 0.021, 95% CI − 0.003 to − 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. Conclusions Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice.https://doi.org/10.1186/s12933-023-02074-1Mitochondrial DNA copy numberCardiometabolic diseaseBidirectionalTwo-sample mendelian randomization study |
| spellingShingle | Pei Qin Tianhang Qin Lei Liang Xinying Li Bin Jiang Xiaojie Wang Jianping Ma Fulan Hu Ming Zhang Dongsheng Hu The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study Cardiovascular Diabetology Mitochondrial DNA copy number Cardiometabolic disease Bidirectional Two-sample mendelian randomization study |
| title | The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study |
| title_full | The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study |
| title_fullStr | The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study |
| title_full_unstemmed | The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study |
| title_short | The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study |
| title_sort | role of mitochondrial dna copy number in cardiometabolic disease a bidirectional two sample mendelian randomization study |
| topic | Mitochondrial DNA copy number Cardiometabolic disease Bidirectional Two-sample mendelian randomization study |
| url | https://doi.org/10.1186/s12933-023-02074-1 |
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