Genetic Relationship Between Ageing and Coronary Heart Disease: a Mendelian Randomization Study

Overview

Journal Eur Geriatr Med

Specialty Geriatrics

Date 2023 Nov 10

PMID 37948032

Authors

Sirun Qin

Zhe Sheng

Chenyang Chen

Yu Cao

Affiliations

Soon will be listed here.

Abstract

Purpose: Genetic relationship between ageing and coronary heart disease has not been well investigated. The aim of the study was to explore the association of several ageing biomarkers with the risk of several types of coronary heart disease using the Mendelian randomization approach.

Methods: Summary data for telomere length, four epigenetic clocks (such as intrinsic epigenetic age acceleration), four types of coronary heart disease (such as myocardial infarction) were collected from the most updated and available genome-wide association studies. Instrumental variables were extracted from the exposure-related summary data according to correlation, independence and exclusivity assumptions. Three Mendelian randomization methods (such as inverse variance weighted) were used for causal inference. Four sensitivity analyses (such as MR-Egger intercept) were performed to prevent horizontal pleiotropy.

Results: Inverse variance weighted reported that longer telomere length was related to the lower risk of myocardial infarction, angina pectoris, unstable angina pectoris and coronary atherosclerosis (P = 8.840e-11, P = 9.830e-04, P = 1.539e-05, P = 2.607e-09). Inverse variance weighted also reported that four epigenetic clocks might be not implicated in the risk of these coronary heart diseases. Furthermore, there was not enough evidence to confirm the effect of coronary heart disease on these ageing biomarkers.

Conclusion: Longer telomere length, but not the epigenetic clock changes, genetically decreased the risk of coronary heart disease. Considering that telomere length and epigenetic clocks were two independent ageing biomarkers, the correlation between ageing and coronary heart disease might be redefined at the genetic level.

Citing Articles

Causal association between epigenetic age acceleration and two pulmonary vascular diseases: pulmonary arterial hypertension and pulmonary embolism-a bidirectional Mendelian study.

Tong J, Wan C, Wang A, Chen M, Ruan B, Shen J Clin Epigenetics. 2024; 16(1):172.

PMID: 39614387 PMC: 11605945. DOI: 10.1186/s13148-024-01778-9.

References

Malta D, Pinheiro P, Vasconcelos N, Stopa S, Vieira M, Lotufo P . Prevalence of Angina Pectoris and Associated Factors in the Adult Population of Brazil: National Survey of Health, 2019. Rev Bras Epidemiol. 2021; 24(suppl 2):e210012. DOI: 10.1590/1980-549720210012.supl.2. View

Chobufo M, Singla A, Rahman E, Osman M, Khan M, Noubiap J . Previously undiagnosed angina pectoris in individuals without established cardiovascular disease: Prevalence and prognosis in the United States. Am J Med Sci. 2022; 364(5):547-553. DOI: 10.1016/j.amjms.2022.06.023. View

Tsai C, Hsieh I, Jeng C, Ho L, Chu P, Chuang S . A decline in the prevalence of angina pectoris: Data from the Nutrition and Health Survey in Taiwan. Int J Cardiol. 2019; 280:1-7. DOI: 10.1016/j.ijcard.2019.01.061. View

Ibrahimou B, Sun N, Azim S, Aliyu M, Guilarte T . Interaction Between Chronic Bronchitis and Blood Cadmium Levels on the Prevalence of Myocardial Infarction in US Adults: The National Health and Nutritional Examination Survey, 2005-2016. J Occup Environ Med. 2021; 63(12):1087-1092. PMC: 8642273. DOI: 10.1097/JOM.0000000000002346. View

Zhao M, Klipstein-Grobusch K, Wang X, Reitsma J, Zhao D, Grobbee D . Prevalence of cardiovascular medication on secondary prevention after myocardial infarction in China between 1995-2015: A systematic review and meta-analysis. PLoS One. 2017; 12(4):e0175947. PMC: 5398555. DOI: 10.1371/journal.pone.0175947. View

Umachandran V, Ranjadayalan K, Ambepityia G, Marchant B, Kopelman P, Timmis A . Aging, autonomic function, and the perception of angina. Br Heart J. 1991; 66(1):15-8. PMC: 1024558. DOI: 10.1136/hrt.66.1.15. View

Sheikh M . Diagnostic Role of Plasma MicroRNA-21 in Stable and Unstable Angina Patients and Association with Aging. Cardiol Res Pract. 2020; 2020:9093151. PMC: 7174930. DOI: 10.1155/2020/9093151. View

Tobin S, Alibhai F, Weisel R, Li R . Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction. Cells. 2020; 9(8). PMC: 7465938. DOI: 10.3390/cells9081894. View

Srinivas N, Rachakonda S, Kumar R . Telomeres and Telomere Length: A General Overview. Cancers (Basel). 2020; 12(3). PMC: 7139734. DOI: 10.3390/cancers12030558. View

10.

Duan R, Fu Q, Sun Y, Li Q . Epigenetic clock: A promising biomarker and practical tool in aging. Ageing Res Rev. 2022; 81:101743. DOI: 10.1016/j.arr.2022.101743. View

11.

Jiang S, Guo Y . Epigenetic Clock: DNA Methylation in Aging. Stem Cells Int. 2020; 2020:1047896. PMC: 7366189. DOI: 10.1155/2020/1047896. View

12.

Xu X, Hu H, Lin Y, Huang F, Ji H, Li Y . Differences in Leukocyte Telomere Length between Coronary Heart Disease and Normal Population: A Multipopulation Meta-Analysis. Biomed Res Int. 2019; 2019:5046867. PMC: 6526555. DOI: 10.1155/2019/5046867. View

13.

Malyutina S, Chervova O, Tillmann T, Maximov V, Ryabikov A, Gafarov V . The Relationship between Epigenetic Age and Myocardial Infarction/Acute Coronary Syndrome in a Population-Based Nested Case-Control Study. J Pers Med. 2022; 12(1). PMC: 8781885. DOI: 10.3390/jpm12010110. View

14.

Birney E . Mendelian Randomization. Cold Spring Harb Perspect Med. 2021; 12(4). PMC: 9121891. DOI: 10.1101/cshperspect.a041302. View

15.

Li W, Wang Z, Hua C, Zhang H, Liu X, Zheng S . Body mass index, frailty, and outcomes in heart failure with preserved ejection fraction. ESC Heart Fail. 2023; 11(2):709-718. PMC: 10966215. DOI: 10.1002/ehf2.14595. View

16.

Codd V, Wang Q, Allara E, Musicha C, Kaptoge S, Stoma S . Polygenic basis and biomedical consequences of telomere length variation. Nat Genet. 2021; 53(10):1425-1433. PMC: 8492471. DOI: 10.1038/s41588-021-00944-6. View

17.

McCartney D, Min J, Richmond R, Lu A, Sobczyk M, Davies G . Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging. Genome Biol. 2021; 22(1):194. PMC: 8243879. DOI: 10.1186/s13059-021-02398-9. View

18.

Burgess S, Small D, Thompson S . A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res. 2015; 26(5):2333-2355. PMC: 5642006. DOI: 10.1177/0962280215597579. View

19.

Emdin C, Khera A, Kathiresan S . Mendelian Randomization. JAMA. 2017; 318(19):1925-1926. DOI: 10.1001/jama.2017.17219. View

20.

Zhang W, Ghosh D . A general approach to sensitivity analysis for Mendelian randomization. Stat Biosci. 2021; 13(1):34-55. PMC: 7962901. DOI: 10.1007/s12561-020-09280-5. View