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High BMI and smoking jointly cause COPD: a Mendelian randomisation study.
Heidi Mikkelsen1,2, Eskild Morten Landt1, Sarah Caroline Weisenfeldt Marott1
1Department of Clinical Biochemistry, Zealand University Hospital Koge, Koge, Denmark.
BMJ Open Respiratory Research
|September 15, 2025
Summary
Genetically high body mass index (BMI) and smoking together increase chronic obstructive pulmonary disease (COPD) risk more than either factor alone. This genetic predisposition highlights a significant combined risk for COPD development.
Area of Science:
- Genetics
- Epidemiology
- Pulmonology
Background:
- Chronic obstructive pulmonary disease (COPD) poses a significant global health burden.
- Understanding the interplay of genetic predisposition and lifestyle factors in COPD development is crucial.
Purpose of the Study:
- To investigate the combined causal effect of genetically high body mass index (BMI) and high tobacco smoking on COPD risk.
- To compare the joint risk of these factors against their individual risks.
Main Methods:
- Utilized two large Danish population-based cohorts with linked health registries.
- Included 112,943 adults genotyped for BMI and smoking-related gene variants.
- Estimated risk ratios for COPD using allele scores for BMI and smoking.
Main Results:
- Both genetically high BMI and smoking individually increased COPD risk.
- The highest COPD risk was observed in individuals with genetic predisposition for both high BMI and smoking.
- Observationally, high cumulative smoking increased COPD risk regardless of BMI.
Conclusions:
- A combination of genetically determined high BMI and tobacco smoking causally increases COPD risk.
- The synergistic effect of these genetic factors elevates COPD risk beyond individual contributions.
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