Impact of birth weight on cardiovascular disease and mediating role of metabolic traits: a Mendelian randomisation study.

Zhuang, J; Chen, S; Long, J; Ding, D; Lam, LT; Li, J; An, R

Impact of birth weight on cardiovascular disease and mediating role of metabolic traits: a Mendelian randomisation study.

Zhuang, J Chen, S Long, J Ding, D Lam, LT Li, J An, R

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Publisher:: BMJ
Publication Type:: Journal Article
Citation:: Open Heart, 2025, 12, (2), pp. e003561
Issue Date:: 2025-10-31

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Field	Value	Language
dc.contributor.author	Zhuang, J
dc.contributor.author	Chen, S
dc.contributor.author	Long, J
dc.contributor.author	Ding, D
dc.contributor.author	Lam, LT
dc.contributor.author	Li, J
dc.contributor.author	An, R
dc.date.accessioned	2026-06-12T01:56:40Z
dc.date.available	2025-10-10
dc.date.available	2026-06-12T01:56:40Z
dc.date.issued	2025-10-31
dc.identifier.citation	Open Heart, 2025, 12, (2), pp. e003561
dc.identifier.issn	2053-3624
dc.identifier.issn	2053-3624
dc.identifier.uri	http://hdl.handle.net/10453/195312
dc.description.abstract	BACKGROUND: Birth weight (BW) has been linked to cardiometabolic diseases, but causal associations with a comprehensive range of cardiovascular outcomes and underlying metabolic mechanisms remain unclear. METHODS: We applied a two-sample Mendelian randomisation (MR) approach to evaluate causal relationships between genetically predicted BW and 16 distinct cardiovascular diseases (CVD). We further conducted a two-step MR mediation analysis to quantify the mediating roles of 24 metabolic traits covering body composition, glucose metabolism, lipid metabolism, blood pressure, fatty acids and amino acids. RESULTS: Genetically lower BW was associated with higher risks of coronary heart disease (OR 0.72, 95% CI 0.65 to 0.81), myocardial infarction (OR 0.71, 95% CI 0.63 to 0.80) and angina pectoris (OR 0.81, 95% CI 0.72 to 0.90). These effects were partly mediated by type 2 diabetes, systolic blood pressure, total cholesterol and triglycerides, explaining 11.76-33.33% of the total associations. In contrast, genetically higher BW increased the risk of aortic aneurysm (OR 1.46, 95% CI 1.21 to 1.75), venous thromboembolism (OR 1.22, 95% CI 1.09 to 1.36) and atrial fibrillation (OR 1.34, 95% CI 1.21 to 1.48). These associations were partly explained by body composition traits, with appendicular lean mass and body mass index mediating 10.53-26.32% of the effect on aortic aneurysm, 15.79-68.42% of the effect on venous thromboembolism and 10.34-58.62% of the effect on atrial fibrillation. CONCLUSIONS: Our study provides robust evidence of distinct causal pathways linking BW with adult cardiovascular risks through specific metabolic mediators. These findings highlight the importance of optimal fetal growth and lifelong metabolic health management as critical strategies to reduce CVD burden.
dc.format	Electronic
dc.language	eng
dc.publisher	BMJ
dc.relation.ispartof	Open Heart
dc.relation.isbasedon	10.1136/openhrt-2025-003561
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.mesh	Humans
dc.subject.mesh	Mendelian Randomization Analysis
dc.subject.mesh	Cardiovascular Diseases
dc.subject.mesh	Birth Weight
dc.subject.mesh	Risk Assessment
dc.subject.mesh	Phenotype
dc.subject.mesh	Infant, Newborn
dc.subject.mesh	Female
dc.subject.mesh	Risk Factors
dc.subject.mesh	Male
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Humans
dc.subject.mesh	Cardiovascular Diseases
dc.subject.mesh	Birth Weight
dc.subject.mesh	Risk Assessment
dc.subject.mesh	Risk Factors
dc.subject.mesh	Phenotype
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Infant, Newborn
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Mendelian Randomization Analysis
dc.subject.mesh	Humans
dc.subject.mesh	Mendelian Randomization Analysis
dc.subject.mesh	Cardiovascular Diseases
dc.subject.mesh	Birth Weight
dc.subject.mesh	Risk Assessment
dc.subject.mesh	Phenotype
dc.subject.mesh	Infant, Newborn
dc.subject.mesh	Female
dc.subject.mesh	Risk Factors
dc.subject.mesh	Male
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.title	Impact of birth weight on cardiovascular disease and mediating role of metabolic traits: a Mendelian randomisation study.
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Health
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-06-12T01:56:38Z
pubs.issue	2
pubs.publication-status	Published online
pubs.volume	12
utslib.citation.issue	2

Abstract:

BACKGROUND: Birth weight (BW) has been linked to cardiometabolic diseases, but causal associations with a comprehensive range of cardiovascular outcomes and underlying metabolic mechanisms remain unclear. METHODS: We applied a two-sample Mendelian randomisation (MR) approach to evaluate causal relationships between genetically predicted BW and 16 distinct cardiovascular diseases (CVD). We further conducted a two-step MR mediation analysis to quantify the mediating roles of 24 metabolic traits covering body composition, glucose metabolism, lipid metabolism, blood pressure, fatty acids and amino acids. RESULTS: Genetically lower BW was associated with higher risks of coronary heart disease (OR 0.72, 95% CI 0.65 to 0.81), myocardial infarction (OR 0.71, 95% CI 0.63 to 0.80) and angina pectoris (OR 0.81, 95% CI 0.72 to 0.90). These effects were partly mediated by type 2 diabetes, systolic blood pressure, total cholesterol and triglycerides, explaining 11.76-33.33% of the total associations. In contrast, genetically higher BW increased the risk of aortic aneurysm (OR 1.46, 95% CI 1.21 to 1.75), venous thromboembolism (OR 1.22, 95% CI 1.09 to 1.36) and atrial fibrillation (OR 1.34, 95% CI 1.21 to 1.48). These associations were partly explained by body composition traits, with appendicular lean mass and body mass index mediating 10.53-26.32% of the effect on aortic aneurysm, 15.79-68.42% of the effect on venous thromboembolism and 10.34-58.62% of the effect on atrial fibrillation. CONCLUSIONS: Our study provides robust evidence of distinct causal pathways linking BW with adult cardiovascular risks through specific metabolic mediators. These findings highlight the importance of optimal fetal growth and lifelong metabolic health management as critical strategies to reduce CVD burden.

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http://hdl.handle.net/10453/195312