Assessing the causal relationship between metabolic biomarkers and coronary artery disease by Mendelian randomization studies

Roth, G. A. et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: Update from the GBD 2019 study. J. Am. Coll. Cardiol. 76, 2982–3021 (2020).Article 
PubMed 
PubMed Central 

Google Scholar 
Timmis, A. et al. European society of cardiology: Cardiovascular disease statistics 2019. Eur. Heart J. 41, 12–85 (2020).Article 
PubMed 

Google Scholar 
Malakar, A. K. et al. A review on coronary artery disease, its risk factors, and therapeutics. J. Cell. Physiol. 234, 16812–16823 (2019).Article 
CAS 
PubMed 

Google Scholar 
Klarin, D. & Natarajan, P. Clinical utility of polygenic risk scores for coronary artery disease. Nat. Rev. Cardiol. 19, 291–301 (2022).Article 
PubMed 

Google Scholar 
Ren, Z., Simons, P. I. H. G., Wesselius, A., Stehouwer, C. D. A. & Brouwers, M. C. G. J. Relationship between NAFLD and coronary artery disease: A Mendelian randomization study. Hepatology 77, 230–238 (2023).Article 
PubMed 

Google Scholar 
Wang, K. et al. Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations. Genome Med. 14, 63 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Liu, H.-M. et al. Sarcopenia-related traits and coronary artery disease: A bi-directional Mendelian randomization study. Aging (Albany NY) 12, 3340–3353 (2020).Article 
PubMed 

Google Scholar 
Bell, S., Gibson, J. T., Harshfield, E. L. & Markus, H. S. Is periodontitis a risk factor for ischaemic stroke, coronary artery disease and subclinical atherosclerosis? A Mendelian randomization study. Atherosclerosis 313, 111–117 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Johnson, C. H., Ivanisevic, J. & Siuzdak, G. Metabolomics: Beyond biomarkers and towards mechanisms. Nat. Rev. Mol. Cell. Biol. 17, 451–459 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Laíns, I. et al. Metabolomics in the study of retinal health and disease. Prog. Retin. Eye Res. 69, 57–79 (2019).Article 
PubMed 

Google Scholar 
Xiao, G. et al. Causality of genetically determined metabolites on anxiety disorders: A two-sample Mendelian randomization study. J. Transl. Med. 20, 475 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gu, Y. et al. Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: A two-sample mendelian randomization study. J. Transl. Med. 21, 357 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ma, Q., Li, Y., An, L., Guo, L. & Liu, X. Assessment of causal association between differentiated thyroid cancer and disordered serum lipid profile: A Mendelian randomization study. Front. Endocrinol. https://doi.org/10.3389/fendo.2023.1291445 (2023).Article 

Google Scholar 
Li, X., Lu, Z., Qi, Y., Chen, B. & Li, B. The role of polyunsaturated fatty acids in osteoarthritis: Insights from a Mendelian randomization study. Nutrients 15, 4787 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Cheng, H. et al. Association of 25-hydroxyvitamin D with preterm birth and premature rupture of membranes: A Mendelian randomization study. Nutrients 15, 3593 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
De La Barrera, B. & Manousaki, D. Serum 25-hydroxyvitamin D levels and youth-onset type 2 diabetes: A two-sample Mendelian randomization study. Nutrients 15, 1016 (2023).Article 
PubMed 

Google Scholar 
Kang, J. et al. The association of lipid metabolism with bone metabolism and the role of human traits: A Mendelian randomization study. Front. Endocrinol. (Lausanne) 14, 1271942 (2023).Article 
PubMed 

Google Scholar 
Liang, H. et al. Causal relationship between linoleic acid and type 2 diabetes and glycemic traits: A bidirectional Mendelian randomization study. Front. Endocrinol. (Lausanne) 14, 1277153 (2023).Article 
PubMed 

Google Scholar 
Doestzada, M. et al. Systematic analysis of relationships between plasma branched-chain amino acid concentrations and cardiometabolic parameters: An association and Mendelian randomization study. BMC Med. 20, 485 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Jia, J. et al. Assessment of causal direction between gut microbiota-dependent metabolites and cardiometabolic health: A bidirectional Mendelian randomization analysis. Diabetes 68, 1747–1755 (2019).Article 
CAS 
PubMed 

Google Scholar 
Li, J. et al. The Mediterranean diet, plasma metabolome, and cardiovascular disease risk. Eur. Heart J. 41, 2645–2656 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gagnon, E. et al. Impact of the gut microbiota and associated metabolites on cardiometabolic traits, chronic diseases and human longevity: A Mendelian randomization study. J. Transl. Med. 21, 60 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Xu, H. et al. Association of circulating branched-chain amino acids with cardiovascular diseases: A Mendelian randomization study. Nutrients 15, 1580 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Chen, Y. et al. Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases. Nat. Genet. 55, 44–53 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Yavorska, O. O. & Burgess, S. MendelianRandomization: An R package for performing Mendelian randomization analyses using summarized data. Int. J. Epidemiol. 46, 1734–1739 (2017).Article 
PubMed 
PubMed Central 

Google Scholar 
van der Harst, P. & Verweij, N. Identification of 64 novel genetic loci provides an expanded view on the genetic architecture of coronary artery disease. Circ. Res. 122, 433–443 (2018).Article 
PubMed 
PubMed Central 

Google Scholar 
Huang, W. et al. Investigating shared genetic architecture between inflammatory bowel diseases and primary biliary cholangitis. JHEP Rep. 6, 101037 (2024).Article 
PubMed 
PubMed Central 

Google Scholar 
Wang, S. et al. Genetically Predicted peripheral immune cells mediate the effect of gut microbiota on influenza susceptibility. Int. J. Mol. Sci. 25, 7706 (2024).Article 
PubMed 
PubMed Central 

Google Scholar 
Slob, E. A. W. & Burgess, S. A comparison of robust Mendelian randomization methods using summary data. Genet. Epidemiol. 44, 313–329 (2020).Article 
PubMed 
PubMed Central 

Google Scholar 
Bowden, J., Davey Smith, G. & Burgess, S. Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression. Int. J. Epidemiol. 44, 512–525 (2015).Article 
PubMed 
PubMed Central 

Google Scholar 
Hartwig, F. P., Davey Smith, G. & Bowden, J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int. J. Epidemiol. 46, 1985–1998 (2017).Article 
PubMed 
PubMed Central 

Google Scholar 
Liu, Q. et al. Exploring risk factors for autoimmune diseases complicated by non-hodgkin lymphoma through regulatory T cell immune-related traits: A Mendelian randomization study. Front. Immunol. 15, 1374938 (2024).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Chen, H. et al. The causal role of gut microbiota in susceptibility and severity of COVID-19: A bidirectional Mendelian randomization study. J. Med. Virol. 95, e28880 (2023).Article 
CAS 
PubMed 

Google Scholar 
Burgess, S. & Thompson, S. G. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur. J. Epidemiol. 32, 377–389 (2017).Article 
PubMed 
PubMed Central 

Google Scholar 
Chong, J. et al. MetaboAnalyst 4.0: Towards more transparent and integrative metabolomics analysis. Nucleic Acids Res. 46, W486–W494 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Clarke, S. L. et al. Coronary artery disease risk of familial hypercholesterolemia genetic variants independent of clinically observed longitudinal cholesterol exposure. Circ. Genom. Precis. Med. 15, e003501 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Santos, R. D. & Shapiro, M. D. Coronary artery calcification and risk stratification in familial hypercholesterolemia: Moving forward but not there yet. JACC Cardiovasc. Imaging 14, 2425–2428 (2021).Article 
PubMed 

Google Scholar 
Girelli, D., Piubelli, C., Martinelli, N., Corrocher, R. & Olivieri, O. A decade of progress on the genetic basis of coronary artery disease. Practical insights for the internist. Eur. J. Intern. Med. 41, 10–17 (2017).Article 
CAS 
PubMed 

Google Scholar 
Langman, L. J. & Cole, D. E. Homocysteine. Crit. Rev. Clin. Lab. Sci. 36, 365–406 (1999).Article 
CAS 
PubMed 

Google Scholar 
Breslow, J. L. Genetics of lipoprotein abnormalities associated with coronary artery disease susceptibility. Annu. Rev. Genet. 34, 233–254 (2000).Article 
CAS 
PubMed 

Google Scholar 
Post, A. et al. Urinary 3-hydroxyisovaleryl carnitine excretion, protein energy malnutrition and risk of all-cause mortality in kidney transplant recipients: Results from the TransplantLines cohort studies. Clin. Nutr. 40, 2109–2120 (2021).Article 
CAS 
PubMed 

Google Scholar 
van Hove, J. L., Rutledge, S. L., Nada, M. A., Kahler, S. G. & Millington, D. S. 3-Hydroxyisovalerylcarnitine in 3-methylcrotonyl-CoA carboxylase deficiency. J. Inherit. Metab. Dis. 18, 592–601 (1995).Article 
PubMed 

Google Scholar 
Röschinger, W. et al. 3-Hydroxyisovalerylcarnitine in patients with deficiency of 3-methylcrotonyl CoA carboxylase. Clin. Chim. Acta 240, 35–51 (1995).Article 
PubMed 

Google Scholar 
Xiong, Y., Jiang, L. & Li, T. Aberrant branched-chain amino acid catabolism in cardiovascular diseases. Front. Cardiovasc. Med. 9, 965899 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Xu, J. et al. Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?. BMC Vet. Res. 12, 114 (2016).Article 
PubMed 
PubMed Central 

Google Scholar 
Rungoe, C., Nyboe Andersen, N. & Jess, T. Inflammatory bowel disease and risk of coronary heart disease. Trends Cardiovasc. Med. 25, 699–704 (2015).Article 
PubMed 

Google Scholar 
Choi, Y. J. et al. Patients with inflammatory bowel disease have an increased risk of myocardial infarction: A nationwide study. Aliment. Pharmacol. Ther. 50, 769–779 (2019).Article 
PubMed 

Google Scholar 
Tsigkas, G. et al. Inflammatory bowel disease: A potential risk factor for coronary artery disease. Angiology 68, 845–849 (2017).Article 
PubMed 

Google Scholar 
Caliskan, Z. et al. Impaired coronary microvascular and left ventricular diastolic function in patients with inflammatory bowel disease. Microvasc. Res. 97, 25–30 (2015).Article 
PubMed 

Google Scholar 
Chen, B. et al. Inflammatory bowel disease and cardiovascular diseases. Am. J. Med. 135, 1453–1460 (2022).Article 
PubMed 

Google Scholar 
Williams, K. A. Nutrition, risk factors, prevention, and imaging: The 2018 Mario Verani Lecture. J. Nucl. Cardiol. 26, 86–91 (2019).Article 
PubMed 

Google Scholar 
Kolwicz, S. C. Ketone body metabolism in the ischemic heart. Front. Cardiovasc. Med. 8, 789458 (2021).Article 
PubMed 
PubMed Central 

Google Scholar 
Hung, P.-L. et al. An examination of serum acylcarnitine and amino acid profiles at different time point of ketogenic diet therapy and their association of ketogenic diet effectiveness. Nutrients 13, 21 (2020).Article 
PubMed 
PubMed Central 

Google Scholar 
Wang, H. et al. Sildenafil treatment in heart failure with preserved ejection fraction: Targeted metabolomic profiling in the RELAX trial. JAMA Cardiol. 2, 896–901 (2017).Article 
PubMed 
PubMed Central 

Google Scholar 
Wu, R., Shen, G., Morris, R., Patnaik, M. & Peter, J. B. Elevated autoantibodies against oxidized palmitoyl arachidonoyl phosphocholine in patients with hypertension and myocardial infarction. J. Autoimmun. 24, 353–360 (2005).Article 
CAS 
PubMed 

Google Scholar 
Karki, P. & Birukov, K. G. Oxidized phospholipids in control of endothelial barrier function: Mechanisms and implication in lung injury. Front. Endocrinol. (Lausanne) 12, 794437 (2021).Article 
PubMed 

Google Scholar 
Appleton, B. D., Palmer, S. A., Smith, H. P., Stephens, L. E. & Major, A. S. Oxidized phospholipid oxPAPC alters regulatory T-cell differentiation and decreases their protective function in atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol. 43, 2119–2132 (2023).Article 
CAS 
PubMed 

Google Scholar 
Zhu, Q. et al. Comprehensive metabolic profiling of inflammation indicated key roles of glycerophospholipid and arginine metabolism in coronary artery disease. Front. Immunol. 13, 829425 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Papageorgiou, N. et al. Asymmetric dimethylarginine as a biomarker in coronary artery disease. Curr. Top. Med. Chem. 23, 470–480 (2023).Article 
CAS 
PubMed 

Google Scholar 
Rodionov, R. N. et al. Homoarginine supplementation prevents left ventricular dilatation and preserves systolic function in a model of coronary artery disease. J. Am. Heart Assoc. 8, e012486 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Wang, B. Y. et al. Dietary arginine prevents atherogenesis in the coronary artery of the hypercholesterolemic rabbit. J. Am. Coll. Cardiol. 23, 452–458 (1994).Article 
CAS 
PubMed 

Google Scholar 
Yin, W.-H. et al. L-arginine improves endothelial function and reduces LDL oxidation in patients with stable coronary artery disease. Clin. Nutr. 24, 988–997 (2005).Article 
CAS 
PubMed 

Google Scholar 
Adams, M. R. et al. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Atherosclerosis 129, 261–269 (1997).Article 
CAS 
PubMed 

Google Scholar 
Das, U. N. Nutritional factors in the prevention and management of coronary artery disease and heart failure. Nutrition 31, 283–291 (2015).Article 
CAS 
PubMed 

Google Scholar 
Karvonen, M. K. et al. Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels. Nat. Med. 4, 1434–1437 (1998).Article 
CAS 
PubMed 

Google Scholar 
Akashi, M., Higashi, T., Masuda, S., Komori, T. & Furuse, M. A coronary artery disease-associated gene product, JCAD/KIAA1462, is a novel component of endothelial cell-cell junctions. Biochem. Biophys. Res. Commun. 413, 224–229 (2011).Article 
CAS 
PubMed 

Google Scholar 
Pu, X. et al. Effect of a coronary-heart-disease-associated variant of ADAMTS7 on endothelial cell angiogenesis. Atherosclerosis 296, 11–17 (2020).Article 
CAS 
PubMed 

Google Scholar 
Wang, J. et al. Proline improves cardiac remodeling following myocardial infarction and attenuates cardiomyocyte apoptosis via redox regulation. Biochem. Pharmacol. 178, 114065 (2020).Article 
CAS 
PubMed 

Google Scholar 
Luo, T. et al. Deficiency of proline/serine-rich coiled-coil protein 1 (PSRC1) accelerates trimethylamine N-oxide-induced atherosclerosis in ApoE-/- mice. J. Mol. Cell. Cardiol. 170, 60–74 (2022).Article 
CAS 
PubMed 

Google Scholar 
Guo, K. et al. PSRC1 overexpression attenuates atherosclerosis progression in apoE-/- mice by modulating cholesterol transportation and inflammation. J. Mol. Cell. Cardiol. 116, 69–80 (2018).Article 
CAS 
PubMed 

Google Scholar