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The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study.
Qin, Pei; Qin, Tianhang; Liang, Lei; Li, Xinying; Jiang, Bin; Wang, Xiaojie; Ma, Jianping; Hu, Fulan; Zhang, Ming; Hu, Dongsheng.
Afiliación
  • Qin P; Department of General Practice, The Affiliated Luohu Hospital of Shenzhen University, No. 47, Youti Road, Shenzhen, 518001, Guangdong, China.
  • Qin T; Institute of Software Chinese Academy of Sciences, Beijing, Guangdong, China.
  • Liang L; Department of Gynecology and Obstetrics, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China.
  • Li X; School of Public Health, Shantou University, Shantou, Guangdong, China.
  • Jiang B; Department of Neurology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China.
  • Wang X; Department of Neurology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China.
  • Ma J; Department of Neurology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China.
  • Hu F; School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China.
  • Zhang M; School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China.
  • Hu D; Department of General Practice, The Affiliated Luohu Hospital of Shenzhen University, No. 47, Youti Road, Shenzhen, 518001, Guangdong, China. dongshenghu563@126.com.
Cardiovasc Diabetol ; 23(1): 45, 2024 01 28.
Article en En | MEDLINE | ID: mdl-38282013
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 (ß= - 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 (ß= - 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Accidente Cerebrovascular / Diabetes Mellitus Tipo 2 / Dislipidemias / Accidente Cerebrovascular Isquémico / Insuficiencia Cardíaca / Hipertensión Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Cardiovasc Diabetol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / ENDOCRINOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Accidente Cerebrovascular / Diabetes Mellitus Tipo 2 / Dislipidemias / Accidente Cerebrovascular Isquémico / Insuficiencia Cardíaca / Hipertensión Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Cardiovasc Diabetol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / ENDOCRINOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido