通过孟德尔随机化研究评估代谢生物标志物与冠状动脉疾病之间的因果关系-动脉网

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

Nature 等信源发布 2024-08-16 02:39



可切换为仅中文







AbstractThe development of coronary artery disease (CAD) is significantly affected by impaired endocrine and metabolic status. Under this circumstance, improved prevention and treatment of CAD may result from knowing the connection between metabolites and CAD. This study aims to delve into the causal relationship between human metabolic biomarkers and CAD by using two-sample Mendelian randomization (MR).

。在这种情况下，了解代谢物与CAD之间的联系可能会改善CAD的预防和治疗。本研究旨在通过使用双样本孟德尔随机化（MR）深入研究人类代谢生物标志物与CAD之间的因果关系。

Utilizing two-sample bidirectional MR analysis, we assessed the correlation between 1400 blood metabolites and CAD, and the metabolites data from the CLSA, encompassing 8299 participants. Metabolite analysis identified 1091 plasma metabolites and 309 ratios as instrumental variables. To evaluate the causal link between metabolites and CAD, we analyzed three datasets: ebi-a-GCST005195 (547,261 European & East Asian samples), bbj-a-159 (29,319 East Asian CAD cases & 183,134 East Asian controls), and ebi-a-GCST005194 (296,525 European & East Asian samples).

利用双样本双向MR分析，我们评估了1400种血液代谢物与CAD之间的相关性，以及来自CLSA的代谢物数据，包括8299名参与者。代谢物分析确定了1091种血浆代谢物和309种比例作为仪器变量。为了评估代谢物与CAD之间的因果关系，我们分析了三个数据集：ebi-a-GCST005195（547261个欧洲和东亚样本），bbj-a-159（29319个东亚CAD病例和183134个东亚对照）和ebi-a-GCST005194（296525个欧洲和东亚样本）。

To estimate causal links, we utilized the IVW method. To conduct sensitivity analysis, we used MR-Egger, Weighted Median, and MR-PRESSO. Additionally, we employed MR-Egger interception and Cochran’s Q statistic to assess potential heterogeneity and pleiotropy. What’s more, replication and reverse analyses were performed to verify the reliability of the results and the causal order between metabolites and disease.

为了估计因果关系，我们使用了IVW方法。为了进行敏感性分析，我们使用了MR-Egger，加权中位数和MR-PRESSO。此外，我们使用MR Egger拦截和Cochran的Q统计量来评估潜在的异质性和多效性。此外，还进行了复制和反向分析，以验证结果的可靠性以及代谢物与疾病之间的因果关系。

Furthermore, we conducted a pathway analysis to identify potential metabolic pathways. 59 blood metabolites and 27 metabolite ratios nominally associated with CAD (P < 0.05) were identified by IVW analysis method. A total of four known blood metabolites, namely beta-hydroxyisovaleroylcarnitine (OR 1.06, 95% CI 1.027–1.094, FDR 0.07), 1-palmitoyl-2-arachidonoyl (OR 1.07, 95% CI 1.029–1.110, FDR 0.09), 1-stearoyl.

此外，我们进行了途径分析，以确定潜在的代谢途径。通过IVW分析方法鉴定了59种血液代谢物和27种与CAD名义相关的代谢物比率（P<0.05）。共有四种已知的血液代谢物，即β-羟基异戊酰基肉碱（OR 1.06，95%CI 1.027-1.094，FDR 0.07），1-棕榈酰基-2-花生四烯酸（OR 1.07，95%CI 1.029-1.110，FDR 0.09），1-硬脂酰基。

IntroductionCoronary artery disease (CAD) is the predominant form of cardiovascular disease, responsible for 9.14 million deaths globally in 20191 CAD poses a significant burden on modern societies, with morbidity and mortality rates comparable to those of cancer2. Despite advancements in pharmacologic and surgical interventions, mortality rates resulting from CAD remain unacceptably high.

引言冠状动脉疾病（CAD）是心血管疾病的主要形式，20191年全球死亡人数为914万CAD对现代社会构成了沉重负担，其发病率和死亡率与癌症相当2。尽管药物和手术干预取得了进展，但CAD导致的死亡率仍然高得令人无法接受。

Effective prevention and treatment of CAD are crucial in reducing morbidity and disability. The exploration of biological mechanisms is essential for achieving this goal, with lifestyle, environmental, and genetic factors being identified as risk factors for cardiovascular disease development3. Over the past decade, significant progress has been made in identifying alleles that increase the risk of CAD4.

有效预防和治疗CAD对于降低发病率和残疾至关重要。探索生物学机制对于实现这一目标至关重要，生活方式，环境和遗传因素被确定为心血管疾病发展的危险因素3。在过去的十年中，在鉴定增加CAD4风险的等位基因方面取得了重大进展。

However, the fundamental mechanisms underlying this complex disease remain incompletely understood. Although etiologic studies of cardiovascular disease have greatly benefited from genetic advancements, particularly genome-wide association studies (GWAS)5,6,7,8, there are still substantial obstacles in linking these genetic discoveries to biological processes.Recent advancements in genomics tools, such as metabolomics, have provided new opportunities to investigate disease pathways.

然而，这种复杂疾病的基本机制仍未完全了解。尽管心血管疾病的病因学研究极大地受益于遗传进展，特别是全基因组关联研究（GWAS）5,6,7,8，但将这些遗传发现与生物过程联系起来仍然存在重大障碍。代谢组学等基因组学工具的最新进展为研究疾病途径提供了新的机会。

Metabolomics, by identifying intermediate metabolites and altered metabolic pathways, can offer new insights into the molecular mechanisms underlying diseases9,10. Global genomic studies of metabolites have recently identified loci associated with diseases, proposing mechanisms for disease onset and disease-related traits11,12,13.

。代谢物的全球基因组研究最近确定了与疾病相关的基因座，提出了疾病发作和疾病相关特征的机制11,12,13。

Moreover, the importance of metabolites in disease is progressively gaining attention, with studies establishing causal relationships between metabolites and delirium, osteoarthr.

此外，代谢物在疾病中的重要性正逐渐受到关注，研究确定了代谢物与deli妄，骨关节炎之间的因果关系。

Data availability

数据可用性

The data required for our analysis were obtained from publicly available data. Data were obtained from IEU OpenGwas (https://gwas.mrcieu.ac.uk/).

我们分析所需的数据是从公开可用的数据中获得的。数据来自IEU OpenGwas(https://gwas.mrcieu.ac.uk/)。

Code availability

代码可用性

All code and software are open source and free of charge. If you need it, you can contact Kai Yang or Yongmei Liu to get.

所有代码和软件都是免费的开源。如果您需要，可以联系杨凯或刘永美获取。

ReferencesRoth, 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).PubMed

。J、美国科罗拉多州。心脏病。762982-3021（2020）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Timmis，A.等人，《欧洲心脏病学会：2019年心血管疾病统计》。《欧洲心脏杂志》41，12–85（2020）。PubMed出版社

Google Scholar

谷歌学者

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

Malakar，A.K.等人，《冠状动脉疾病及其危险因素和治疗的综述》。J、细胞。生理学。23416812-16823（2019）。中科院

PubMed

Google Scholar

谷歌学者

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

Klarin，D。＆Natarajan，P。冠状动脉疾病多基因风险评分的临床应用。国家心脏病修订版。19291-301（2022）。PubMed出版社

Google Scholar

谷歌学者

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).PubMed

Ren，Z.，Simons，P.I.H.G.，Wesselius，A.，Stehouwer，C.D.A.＆Brouwers，M.C.G.J.NAFLD与冠状动脉疾病之间的关系：孟德尔随机研究。。PubMed出版社

Google Scholar

谷歌学者

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).CAS

Wang，K.等人。东亚和欧洲人群37个临床因素和冠状动脉疾病的孟德尔随机分析。基因组医学14,63（2022）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

Liu，H.-M.等人。肌肉减少症相关特征与冠状动脉疾病：双向孟德尔随机研究。老龄化（纽约州奥尔巴尼）123340-3353（2020）。PubMed出版社

Google Scholar

谷歌学者

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).CAS

Bell，S.，Gibson，J.T.，Harshfield，E.L。和Markus，H.S。牙周炎是缺血性中风，冠状动脉疾病和亚临床动脉粥样硬化的危险因素吗？孟德尔随机研究。动脉粥样硬化313111-117（2020）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Johnson，C.H.，Ivanisevic，J。＆Siuzdak，G。代谢组学：超越生物标志物和机制。自然修订摩尔电池。生物学17451-459（2016）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Laíns，I.等人，《视网膜健康与疾病研究中的代谢组学》。程序。雷丁。Eye Res.69,57-79（2019）。PubMed出版社

Google Scholar

谷歌学者

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

Xiao，G.等人。遗传决定代谢物对焦虑症的因果关系：双样本孟德尔随机研究。J、翻译。医学杂志20475（2022）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

Gu，Y.等人。遗传决定的代谢物和代谢途径对骨关节炎的因果关系：双样本孟德尔随机研究。J、翻译。医学杂志21357（2023）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Ma，Q.，Li，Y.，An，L.，Guo，L。＆Liu，X。评估分化型甲状腺癌与血脂异常之间的因果关系：孟德尔随机研究。正面。内分泌。https://doi.org/10.3389/fendo.2023.1291445（2023年）。文章

Google Scholar

谷歌学者

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).CAS

Li，X.，Lu，Z.，Qi，Y.，Chen，B。＆Li，B。多不饱和脂肪酸在骨关节炎中的作用：来自孟德尔随机研究的见解。。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

Cheng，H.等人。25-羟基维生素D与早产和胎膜早破的关系：孟德尔随机研究。营养素153593（2023）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

De La Barrera，B。＆Manousaki，D。血清25-羟基维生素D水平和青少年发病的2型糖尿病：两样本孟德尔随机研究。营养素151016（2023）。PubMed出版社

Google Scholar

谷歌学者

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).PubMed

Kang，J.等人。脂质代谢与骨代谢的关系以及人类特征的作用：孟德尔随机研究。正面。内分泌。。PubMed出版社

Google Scholar

谷歌学者

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).PubMed

Liang，H.等人。亚油酸与2型糖尿病和血糖性状之间的因果关系：双向孟德尔随机研究。正面。内分泌。（洛桑）141277153（2023）。PubMed出版社

Google Scholar

谷歌学者

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).CAS

Doestzada，M.等人。血浆支链氨基酸浓度与心脏代谢参数之间关系的系统分析：关联和孟德尔随机化研究。BMC Med.20485（2022）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

Jia，J.等人。肠道微生物群依赖性代谢物与心脏代谢健康之间因果方向的评估：双向孟德尔随机化分析。糖尿病681747-1755（2019）。中科院

PubMed

Google Scholar

谷歌学者

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

Li，J。等人。地中海饮食，血浆代谢组和心血管疾病风险。。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

肠道微生物群和相关代谢物对心脏代谢特征、慢性疾病和人类寿命的影响：孟德尔随机研究。J、翻译。医学杂志21，60（2023）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Xu，H.等人。循环支链氨基酸与心血管疾病的关联：孟德尔随机研究。营养素151580（2023）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Chen，Y.等人，《血浆代谢组基因组图谱》优先考虑与人类疾病有关的代谢物。纳特·吉内特。55，44-53（2023）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Yavorska，O。O。和Burgess，S。MendelianRandomization：使用汇总数据进行孟德尔随机化分析的R包。国际流行病学杂志。461734-1739（2017）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

van der Harst，P。＆Verweij，N。鉴定64个新的基因位点为冠状动脉疾病的遗传结构提供了扩展的观点。。第122433-443号决议（2018年）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Huang，W.等人。研究炎症性肠病和原发性胆汁性胆管炎之间的共同遗传结构。JHEP代表6101037（2024）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

Wang，S.等人。基因预测的外周免疫细胞介导肠道微生物群对流感易感性的影响。Int.J.Mol.Sci。257706（2024）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Slob，E.A.W.＆Burgess，S。使用汇总数据比较稳健的孟德尔随机化方法。基因。流行病。44313-329（2020）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

。国际流行病学杂志。44512-525（2015）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

Hartwig，F.P.，Davey-Smith，G。＆Bowden，J。通过零模态多效性假设在汇总数据孟德尔随机化中进行稳健推断。国际流行病学杂志。461985-1998（2017）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

Liu，Q.等。通过调节性T细胞免疫相关性状探索自身免疫性疾病并发非霍奇金淋巴瘤的危险因素：孟德尔随机研究。正面。免疫。151374938（2024）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

Chen，H.等人。肠道微生物群在新型冠状病毒肺炎易感性和严重程度中的因果作用：双向孟德尔随机研究。J、医学博士Virol。95，e28880（2023）。中科院

PubMed

Google Scholar

谷歌学者

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

Burgess，S.＆Thompson，S.G.使用MR-Egger方法解释孟德尔随机化的发现。欧洲流行病学杂志。32377-389（2017）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Chong，J.等人，《MetaboAnalyst 4.0：走向更透明和综合的代谢组学分析》。核酸研究46，W486–W494（2018）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

Clarke，S.L.等人。家族性高胆固醇血症遗传变异的冠状动脉疾病风险与临床观察到的纵向胆固醇暴露无关。。基因组。精确。医学杂志15，e003501（2022）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

。JACC心血管。成像142425-2428（2021）。PubMed出版社

Google Scholar

谷歌学者

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).CAS

Girelli，D.，Piubelli，C.，Martinelli，N.，Corrocher，R。＆Olivieri，O。冠状动脉疾病遗传基础的十年进展。内科医生的实用见解。Eur.J.实习生。医学杂志41,10-17（2017）。中科院

PubMed

Google Scholar

谷歌学者

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

Langman，L.J。和Cole，D.E。同型半胱氨酸。暴击。修订临床。实验室科学。。中科院

PubMed

Google Scholar

谷歌学者

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

Breslow，J.L。与冠状动脉疾病易感性相关的脂蛋白异常的遗传学。年。Genet牧师。34233-254（2000）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

Post，A.等人，《肾移植受者尿中3-羟基异戊基肉碱排泄、蛋白质能量营养不良和全因死亡风险：移植系队列研究的结果》。临床。营养。402109-2120（2021）。中科院

PubMed

Google Scholar

谷歌学者

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).PubMed

van Hove，J.L.，Rutledge，S.L.，Nada，M.A.，Kahler，S.G。和Millington，D.S。3-羟基异戊酰肉碱在3-甲基巴豆酰辅酶A羧化酶缺乏症中的作用。J、继承.Metab。Dis。18592-601（1995）。PubMed出版社

Google Scholar

谷歌学者

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

Röschinger，W。等人。3-羟基异戊基肉碱治疗3-甲基巴豆酰辅酶A羧化酶缺乏症患者。临床。奇姆。Acta 240，35–51（1995）。PubMed出版社

Google Scholar

谷歌学者

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

Xiong，Y.，Jiang，L。＆Li，T。心血管疾病中异常的支链氨基酸分解代谢。正面。心血管。医学杂志9965899（2022）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Xu，J.等人。犬炎症性肠病是否影响肠道微生物特征和宿主代谢？。BMC兽医。第12114（2016）号决议。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Rungoe，C.，Nyboe-Andersen，N。＆Jess，T。炎症性肠病和冠心病的风险。。医学25699-704（2015）。PubMed出版社

Google Scholar

谷歌学者

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).PubMed

Choi，Y.J.等人。炎症性肠病患者心肌梗死风险增加：一项全国性研究。食物。药理学。。50769-779（2019）。PubMed出版社

Google Scholar

谷歌学者

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

Tsigkas，G。等人。炎症性肠病：冠状动脉疾病的潜在危险因素。血管学68845-849（2017）。PubMed出版社

Google Scholar

谷歌学者

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

。微血管。第97、25–30号决议（2015年）。PubMed出版社

Google Scholar

谷歌学者

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

Chen，B。等人。炎症性肠病和心血管疾病。《美国医学杂志》1351453-1460（2022）。PubMed出版社

Google Scholar

谷歌学者

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

Williams，K.A。营养，危险因素，预防和成像：2018年马里奥·维拉尼讲座。J、核。心脏病。26,86-91（2019）。PubMed出版社

Google Scholar

谷歌学者

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

Kolwicz，S.C。缺血心脏中的酮体代谢。正面。心血管。医学杂志8789458（2021）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

Hung，P.-L.等人。生酮饮食治疗不同时间点血清酰基肉碱和氨基酸谱的检查及其与生酮饮食有效性的关系。营养素13,21（2020）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).PubMed

Wang，H.等人。射血分数保留的心力衰竭的西地那非治疗：RELAX试验中的靶向代谢组学分析。JAMA Cardiol公司。2896-901（2017）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

Wu，R.，Shen，G.，Morris，R.，Patnaik，M。＆Peter，J.B。高血压和心肌梗塞患者对氧化棕榈酰花生四烯酸磷酸胆碱的自身抗体升高。J、自身免疫。24353-360（2005）。中科院

PubMed

Google Scholar

谷歌学者

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).PubMed

Karki，P。＆Birukov，K.G。氧化磷脂控制内皮屏障功能：肺损伤的机制和意义。正面。内分泌。（洛桑）12794437（2021）。PubMed出版社

Google Scholar

谷歌学者

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).CAS

Appleton，B.D.，Palmer，S.A.，Smith，H.P.，Stephens，L.E.＆Major，A.S。氧化磷脂oxPAPC改变调节性T细胞分化并降低其在小鼠动脉粥样硬化中的保护功能。动脉硬化。血栓。Vasc。生物学432119-2132（2023）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

Zhu，Q。等人。炎症的综合代谢谱表明甘油磷脂和精氨酸代谢在冠状动脉疾病中的关键作用。正面。免疫。。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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

Papageorgiou，N。等人。不对称二甲基精氨酸作为冠状动脉疾病的生物标志物。货币。顶部。医学化学。23470–480（2023）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

Rodionov，R.N。等人。在冠状动脉疾病模型中，补充高精氨酸可防止左心室扩张并保留收缩功能。J、美国心脏协会第8号，e012486（2019）。中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).CAS

Wang，B.Y.等人。膳食精氨酸可预防高胆固醇血症兔冠状动脉的动脉粥样硬化形成。J.Am.Coll。心脏病。23452-458（1994）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

Yin，W.-H.等人。L-精氨酸改善稳定型冠状动脉疾病患者的内皮功能并降低LDL氧化。临床。营养。24988-997（2005）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

Adams，M.R.等人。口服L-精氨酸可改善年轻冠心病患者的内皮依赖性扩张并降低单核细胞与内皮细胞的粘附。动脉粥样硬化129261-269（1997）。中科院

PubMed

Google Scholar

谷歌学者

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

联合国营养因素在预防和管理冠状动脉疾病和心力衰竭中的作用。营养学31283-291（2015）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

Karvonen，M.K.等人。神经肽Y信号肽中亮氨酸（7）-脯氨酸（7）多态性与高血清胆固醇和低密度脂蛋白胆固醇水平的关联。《自然医学》41434-1437（1998）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

明石，M.，东，T.，Masuda，S.，小森，T。＆Furuse，M。冠状动脉疾病相关基因产物JCAD/KIAA1462是内皮细胞-细胞连接的新型成分。生物化学。生物物理。公共资源。413224-229（2011）。中科院

PubMed

Google Scholar

谷歌学者

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

Pu，X。等人。冠心病相关的ADAMTS7变体对内皮细胞血管生成的影响。动脉粥样硬化296,11-17（2020）。中科院

PubMed

Google Scholar

谷歌学者

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

Wang，J。等人。脯氨酸改善心肌梗塞后的心脏重塑，并通过氧化还原调节减弱心肌细胞凋亡。生物化学。药理学。178114065（2020）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

Luo，T。等人。富含脯氨酸/丝氨酸的卷曲螺旋蛋白1（PSRC1）的缺乏加速了ApoE-/-小鼠中三甲胺N-氧化物诱导的动脉粥样硬化。J、摩尔电池。心脏病。170，60-74（2022）。中科院

PubMed

Google Scholar

谷歌学者

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).CAS

Guo，K。等人。PSRC1过表达通过调节胆固醇转运和炎症来减弱apoE-/-小鼠的动脉粥样硬化进展。J、摩尔电池。心脏病。116,69-80（2018）。中科院

PubMed

Google Scholar

谷歌学者

Download referencesAuthor informationAuthor notesThese authors contributed equally: Kai Yang and Jixin Li.Authors and AffiliationsGuang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaKai Yang, Xiaoshan Hui & Yongmei LiuXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of ChinaJixin Li & Wenru WangShandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of ChinaKai YangAuthorsKai YangView author publicationsYou can also search for this author in.

下载参考文献作者信息作者注意到这些作者做出了同样的贡献：杨凯和李继新。作者和附属机构中国中医科学院广安门医院，北京，100053，中华人民共和国杨凯，萧山惠和永美刘西苑医院，中国中医科学院，北京，100091，中华人民共和国李继新和王文如山东中医药大学，济南，250355，中华人民共和国杨凯作者杨凯观点作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarJixin LiView author publicationsYou can also search for this author in

PubMed Google ScholarJixin LiView作者出版物您也可以在

PubMed Google ScholarXiaoshan HuiView author publicationsYou can also search for this author in

PubMed谷歌学者萧山回眸作者出版物您也可以在

PubMed Google ScholarWenru WangView author publicationsYou can also search for this author in

PubMed Google ScholarWenru WangView作者出版物您也可以在

PubMed Google ScholarYongmei LiuView author publicationsYou can also search for this author in

PubMed Google ScholaryYongmei LiuView作者出版物您也可以在

PubMed Google ScholarContributionsFormal analysis, X.H; Methodology, K.Y, J.L and Y.L; Software, J.L and W.W; Supervision, Y. L; Validation, X.H; Writing—original draft, K.Y; Writing—review & editing, Y.L. The results were discussed and the text was evaluated by all authors.Corresponding authorCorrespondence to.

PubMed谷歌学术贡献规范分析，X.H；方法论，K.Y，J.L和Y.L；软件，J.L和W.W；监督，Y.L；验证，X.H；撰写原稿，K.Y；写作评论与编辑，Y.L。讨论了结果，所有作者都对文本进行了评估。对应作者对应。

Yongmei Liu.Ethics declarations

刘永梅。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Additional informationPublisher's noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary InformationSupplementary Figures.Supplementary Tables.Rights and permissions

Additional informationPublisher的noteSpringer Nature在已发布地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充数字。补充表格。权限和权限

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

开放获取本文是根据知识共享署名非商业性NoDerivatives 4.0国际许可证授权的，该许可证允许以任何媒介或格式进行任何非商业性使用，共享，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出您是否修改了许可材料。

You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by-nc-nd/4.0/..

Reprints and permissionsAbout this articleCite this articleYang, K., Li, J., Hui, X. et al. Assessing the causal relationship between metabolic biomarkers and coronary artery disease by Mendelian randomization studies.

转载和许可本文引用本文Yang，K.，Li，J.，Hui，X。等人通过孟德尔随机研究评估代谢生物标志物与冠状动脉疾病之间的因果关系。

Sci Rep 14, 19034 (2024). https://doi.org/10.1038/s41598-024-69879-2Download citationReceived: 27 February 2024Accepted: 09 August 2024Published: 16 August 2024DOI: https://doi.org/10.1038/s41598-024-69879-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1419034（2024）。https://doi.org/10.1038/s41598-024-69879-2Download引文收到日期：2024年2月27日接受日期：2024年8月9日发布日期：2024年8月16日OI：https://doi.org/10.1038/s41598-024-69879-2Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

KeywordsCardiovascular diseasePlasma metabolitesMendelian randomizationBiomarkerRisk assessment

关键词心血管疾病血浆代谢物指数随机化生物标志物风险评估

CommentsBy submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

评论通过提交评论，您同意遵守我们的条款和社区指南。如果您发现有虐待行为或不符合我们的条款或准则，请将其标记为不合适。

全球产业链接平台

重庆市渝北区金星科技大厦A区5楼512室

联系电话：023-67139735（重庆）

关于我们

产品服务