Lee Mia D, Voight Benjamin F
Pharmacology Graduate Group, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA, USA.
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA, USA.
Atheroscler Plus. 2025 May 7;60:43-50. doi: 10.1016/j.athplu.2025.04.002. eCollection 2025 Jun.
Susceptibility to cardiovascular disease (CVD) is driven by genetic and environmental risk factors. Diet is a modifiable and largely environmental risk factor for CVD. Genetic factors associated with a variety of dietary preferences revealed via recent genome-wide association studies (GWAS) allow further investigate the role of diet in liability to disease that has been limited to observational and epidemiologic studies with mixed findings.
We obtained publicly available genome-wide association data for 38 dietary preference traits and seven common CVDs to investigate causal hypotheses between diet as the exposure to CVD as outcomes using the statistical framework of Mendelian randomization (MR) for hypothesis testing and sensitivity analyses. We also conducted mediation analyses to evaluate the effects of dietary preferences on CVDs to elucidate potential causal graphs and estimate the effects of dietary preferences mediated by potential mediators.
Across all methods, we identified 10 significant causal effects, which included eight dietary preferences across three CVD endpoints (Bonferroni-corrected P < 1.88 × 10). In sensitivity MR and mediation analysis, we observed that obesity - quantified by body mass index (BMI) - was a common mediator that contributed to many of these observed effects. We also found that educational attainment was an exclusive, additional mediator for the effect of preference for muesli with risk to peripheral artery disease (PAD).
Our results provide genetic evidence for a link between diet and CVD that aligns with obesity-mediated risk of CVD in individuals in relation to their specific preferences for food.
心血管疾病（CVD）的易感性由遗传和环境风险因素驱动。饮食是一种可改变的且在很大程度上属于环境的CVD风险因素。通过近期全基因组关联研究（GWAS）揭示的与多种饮食偏好相关的遗传因素，使得我们能够进一步研究饮食在疾病易感性中的作用，而此前这一作用仅限于结果混杂的观察性和流行病学研究。
我们获取了公开可用的关于38种饮食偏好特征和7种常见CVD的全基因组关联数据，使用孟德尔随机化（MR）的统计框架进行假设检验和敏感性分析，以研究作为暴露因素的饮食与作为结局的CVD之间的因果假设。我们还进行了中介分析，以评估饮食偏好对CVD的影响，从而阐明潜在的因果关系图，并估计由潜在中介因素介导的饮食偏好的影响。
在所有方法中，我们确定了10个显著的因果效应，其中包括在三个CVD终点的8种饮食偏好（经Bonferroni校正的P < 1.88×10）。在敏感性MR和中介分析中，我们观察到以体重指数（BMI）量化的肥胖是一个常见的中介因素，它促成了许多这些观察到的效应。我们还发现，受教育程度是燕麦片偏好与外周动脉疾病（PAD）风险之间关系的一个独特的额外中介因素。
我们的结果为饮食与CVD之间的联系提供了遗传证据，这与个体因对食物的特定偏好而导致的肥胖介导的CVD风险相一致。
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