Growing evidence suggests that relative carbohydrate intake affects depression; however, the association between carbohydrates and depression remains controversial. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using genetic variants associated with relative carbohydrate intake (N = 268,922) and major depressive disorder (N = 143,265) from the largest available genome-wide association studies. MR evidence suggested a causal relationship between higher relative carbohydrate intake and lower depression risk (odds ratio, 0.42 for depression per one-standard-deviation increment in relative carbohydrate intake; 95% confidence interval, 0.28 to 0.62; P = 1.49 × 10⁻⁵). Multivariable MR indicated that the protective effect of relative carbohydrate intake on depression persisted after conditioning on other diet compositions. The mediation analysis via two-step MR showed that this effect was partly mediated by body mass index, with a mediated proportion of 15.4% (95% confidence interval, 6.7% to 24.1%). These findings may inform prevention strategies and interventions directed towards relative carbohydrate intake and depression.

越来越多的证据表明，碳水化合物的相对摄入量会影响抑郁症；然而，碳水化合物与抑郁症之间的关联仍存在争议。 为了测试这一点，我们使用最大的可用全基因组关联研究中与相对碳水化合物摄入量 ( N  = 268,922) 和重度抑郁症 ( N = 143,265)相关的遗传变异进行了双样本双向孟德尔随机化 (MR) 分析。MR 证据表明较高的相对碳水化合物摄入量与较低的抑郁症风险之间存在因果关系（比值比，相对碳水化合物摄入量每增加一个标准差，抑郁症的比值比为 0.42；95% 置信区间，0.28 至 0.62；P  = 1.49 × 10 ^-5). 多变量 MR 表明，相对碳水化合物摄入量对抑郁症的保护作用在对其他饮食成分进行调节后仍然存在。通过两步 MR 进行的中介分析表明，这种效应部分由体重指数介导，介导比例为 15.4%（95% 置信区间，6.7% 至 24.1%）。这些发现可能会为针对相对碳水化合物摄入量和抑郁症的预防策略和干预措施提供信息。