Evidence map›Paper›PMID 39113039›Full record

ArticleRespiratory research2024

Mendelian randomization study on causal association of TEF and circadian rhythm with pulmonary arterial hypertension.

Dandan Chen, Qi Jin, Lifan Yang, Xiaochun Zhang, Mingfei Li, Lei Zhang, Wenzhi Pan, Daxin Zhou, Junbo Ge, Lihua Guan

Abstract read
In one paragraph

Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Dandan Chen *Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
Qi Jin *Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
Lifan YangDepartment of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
Xiaochun ZhangDepartment of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
Mingfei LiDepartment of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
Lei ZhangDepartment of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
Wenzhi PanDepartment of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
Daxin ZhouDepartment of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. zhou.daxin@zs-hospital.sh.cn.
Junbo GeDepartment of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. jbge@zs-hospital.sh.cn.
Lihua GuanDepartment of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. guanlihua2023@163.com.

Funding

the National Natural Science Foundation for youth of China 82200062the Yangfan Project of Science and Technology Commission of Shanghai Municipality 22YF1439500the Youth Fund of Zhongshan Hospital, Fudan University 2021-016
6 · The paper itself

Abstract

backgroundPrevious research has revealed the potential impact of circadian rhythms on pulmonary diseases; however, the connection between circadian rhythm-associated Thyrotroph Embryonic Factor (TEF) and Pulmonary Arterial Hypertension (PAH) remains unclear. We aim to assess the genetic causal relationship between TEF and PAH by utilizing two sets of genetic instrumental variables (IV) and publicly available Pulmonary Arterial Hypertension Genome-Wide Association Studies (GWAS).

methodsTotal of 23 independent TEF genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Gain- and loss-of-function experiments were used to demonstrate the role of TEF in PAH.

resultsOur analysis revealed that as TEF levels increased genetically, there was a corresponding increase in the risk of PAH, as evidenced by IVW (OR = 1.233, 95% CI: 1.054-1.441; P = 0.00871) and weighted median (OR = 1.292, 95% CI for OR: 1.064-1.568; P = 0.00964) methods. Additionally, the up-regulation of TEF expression was associated with a significantly higher likelihood of abnormal circadian rhythm (IVW: P = 0.0024733, β = 0.05239). However, we did not observe a significant positive correlation between circadian rhythm and PAH (IVW: P = 0.3454942, β = 1.4980398). In addition, our in vitro experiments demonstrated that TEF is significantly overexpressed in pulmonary artery smooth muscle cells (PASMCs). And overexpression of TEF promotes PASMC viability and migratory capacity, as well as upregulates the levels of inflammatory cytokines.

conclusionOur analysis suggests a causal relationship between genetically increased TEF levels and an elevated risk of both PAH and abnormal circadian rhythm. Consequently, higher TEF levels may represent a risk factor for individuals with PAH.

Indexed as

Circadian RhythmGenome-Wide Association StudyMendelian Randomization AnalysisFemaleHumansMalePulmonary Arterial HypertensionCircadian rhythmGWASMendelian randomization (MR)Pulmonary arterial hypertension (PAH)Thyrotroph embryonic factor (TEF)

Identifiers

PMID39113039
PMCPMC11308427

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.