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Birth Weight, Cardiometabolic Factors, and Coronary Heart Disease: A Mendelian Randomization Study

Shuyao Su1, Jingwen Fan1, Yongli Yang1

  • 1Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.

The Journal of Clinical Endocrinology and Metabolism
|May 29, 2023
PubMed

Insights

Lower birth weight (BW) increases coronary heart disease (CHD) risk, with both fetal and maternal BW contributing. Cardiometabolic factors like blood pressure mediate this causal link.

Area of Science:

  • Cardiovascular Epidemiology
  • Genetics
  • Metabolic Health

Background:

  • Observational studies suggest a link between birth weight (BW) and coronary heart disease (CHD), but findings are inconsistent.
  • Existing research cannot differentiate between fetal and maternal influences on BW and their respective impacts on CHD risk.

Purpose of the Study:

  • To investigate the causal relationship between BW and CHD.
  • To disentangle the fetal versus maternal contributions to BW-related CHD risk.
  • To quantify the mediating roles of cardiometabolic factors in the BW-CHD association.

Main Methods:

  • Utilized two-sample Mendelian randomization (MR) with genome-wide association study summary data for BW (own and offspring) and 16 cardiometabolic factors.
  • Employed MR-Egger and inverse variance weighted (IVW) methods to estimate causal effects.
  • Conducted two-step MR mediation analyses to assess the role of cardiometabolic factors.

Main Results:

  • Lower BW was causally associated with increased CHD risk (IVW β = -0.30).
  • Both fetal-specific and maternal-specific BW showed similar inverse associations with CHD risk.
  • Five mediators were identified: hip circumference, triglycerides, fasting insulin, diastolic blood pressure, and systolic blood pressure (SBP), mediating 7.44%–27.75% of the effect.

Conclusions:

  • Lower BW is a causal risk factor for CHD.
  • Both fetal and maternal BW contribute to CHD risk.
  • The causal pathway from BW to CHD is significantly mediated by cardiometabolic factors, particularly SBP and glycemic factors.
Abstract

Keywords:
Mendelian randomizationbirth weightcardiometabolic factorscoronary heart disease

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