Bidirectional two-sample Mendelian randomization analysis identifies causal associations between relative carbohydrate intake and depression

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 x 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. Using genomic data and Mendelian randomization techniques, Yao and coauthors show that higher relative carbohydrate intake may have a protective effect, lowering depression risk.

Automated summary

Research suggests that there is a causal relationship between higher relative carbohydrate intake and lower depression risk. This protective effect is partly mediated by body mass index.