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Low Intelligence Predicts Higher Risks of Coronary Artery Disease and Myocardial Infarction: Evidence From Mendelian
Fangkun Yang1, Teng Hu2, Songzan Chen3
1Department of Cardiology, Ningbo Hospital of Zhejiang University (Ningbo First Hospital), School of Medicine, Zhejiang University, Ningbo, China.
Insights
Higher intelligence is causally linked to a lower risk of coronary artery disease (CAD) and myocardial infarction (MI). This genetic study suggests intelligence may protect against heart disease.
Area of Science:
- Genetics
- Cardiovascular Epidemiology
- Psychometrics
Background:
- Observational studies suggest a link between lower intelligence and increased cardiovascular disease risk.
- The causal nature of this association remains uncertain.
- Investigating the genetic basis of intelligence and its impact on cardiovascular health is crucial.
Purpose of the Study:
- To determine the causal relationship between intelligence and coronary artery disease (CAD).
- To investigate the causal relationship between intelligence and myocardial infarction (MI).
- To utilize Mendelian randomization to infer causality.
Main Methods:
- A two-sample Mendelian randomization study design.
- Utilized 121 single nucleotide polymorphisms as genetic instrumental variables for intelligence.
- Employed summary statistics from large-scale genome-wide association studies (CARDIoGRAMplusC4D and FinnGen) for CAD and MI.
Main Results:
- Genetically predicted higher intelligence was associated with a significantly lower risk of CAD (OR, 0.76) and MI (OR, 0.78).
- Results were robust across sensitivity analyses and replicated in independent datasets.
- MR-Egger tests indicated no significant directional pleiotropy.
Conclusions:
- This Mendelian randomization study provides strong genetic evidence for a causal link between higher intelligence and reduced risk of CAD and MI.
- The findings suggest that intelligence may have a protective effect against cardiovascular diseases.
- Further research into the biological mechanisms underlying this association is warranted.
Abstract:
Background: Low intelligence has been shown to be associated with a high risk of cardiovascular disease in observational studies. It remains unclear whether the association is causal. This study aimed to explore the causal association of intelligence with coronary artery disease (CAD) and myocardial infarction (MI). Methods: A two-sample Mendelian randomization study was designed to infer the causality. A total of 121 single nucleotide polymorphisms were selected as a genetic instrumental variable for intelligence. Summary data on CAD (n = 184,305) and MI (n = 171,875) were obtained from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium and the FinnGen study. Inverse variance weighting method was used to calculate the effect estimates. Sensitivity analyses including other statistical models and leave-one-out analysis were conducted to verify the robustness of results. MR-Egger test was performed to assess the pleiotropy. Results: Genetically predicted higher intelligence was significantly associated with lower risk of CAD (OR, .76; 95%CI, .69-.85; p = 1.5 × 10-7) and MI (OR, .78; 95%CI, .70-.87; p = 7.9 × 10-6). The results remained consistent in the majority of the sensitivity analyses and were repeated in the FinnGen datasets. MR-Egger test suggested no evidence of directional pleiotropy for the association with coronary artery disease (intercept = -.01, p = .19) and myocardial infarction (intercept = -.01, p = .06). Conclusion: This Mendelian randomization analysis provided genetic evidence for the causal association between low intelligence and increased risks of CAD and MI.
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