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Causal association of modifiable factors with cardiometabolic multimorbidity: an exposome-wide Mendelian

Dun Li1, Jing Lin2, Hongxi Yang3

  • 1School of Public Health, Tianjin Medical University, Tianjin, 300070, China.

Cardiovascular Diabetology
|June 6, 2025
PubMed

Insights

This study identifies key modifiable factors influencing cardiometabolic multimorbidity (CMM). Promoting education and healthy lifestyle choices like avoiding smoking and sedentary behavior can prevent CMM and related diseases.

Area of Science:

  • Genetics and Epidemiology
  • Public Health
  • Cardiovascular and Metabolic Diseases

Background:

  • Cardiometabolic multimorbidity (CMM), the co-occurrence of multiple cardiometabolic diseases (CMDs), is a significant global health issue.
  • Causal links between modifiable factors and CMDs/CMM require systematic investigation.

Purpose of the Study:

  • To systematically investigate the causal associations of various modifiable factors with cardiometabolic multimorbidity (CMM) and individual cardiometabolic diseases (CMDs).
  • To identify key risk and protective factors for CMM and CMDs using a Mendelian randomization approach.

Main Methods:

  • Employed a three-stage Mendelian randomization (MR) design, including two-sample MR with sample overlap correction and multivariable MR.
  • Examined modifiable factors across socioeconomic, behavioral, biochemical, and physical domains as exposures.
  • Utilized updated, large-scale genome-wide association study (GWAS) data from the GWAS Catalog.

Main Results:

  • Thirteen of 23 modifiable factors demonstrated robust associations with CMM, including educational attainment, household income, smoking, screen time, lipid levels, fasting glucose, HbA1c, blood pressure, FEV1, and BMI.
  • Independent associations with CMM were found for household income, smoking, HbA1c, systolic blood pressure, and FEV1.
  • Multi-response MR confirmed associations for educational attainment, serum urate, and BMI with CMM, and smoking, physical activity, and screen time with various CMDs.

Conclusions:

  • Prioritizing educational attainment, maintaining healthy serum urate levels, and controlling obesity are crucial for CMM prevention.
  • Avoiding smoking, sedentary behavior, and increasing physical activity offer significant protection against CMDs.
  • Improving dyslipidemia, dysglycemia, blood pressure, and lung function aids in co-managing CMDs and preventing CMM.
Abstract

Keywords:
Cardiometabolic diseasesCardiometabolic multimorbidityCausal inferenceMendelian randomizationModifiable factor

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