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

Shi Yao, Meng Zhang, Shan-Shan Dong, Jia-Hao Wang, Kun Zhang, Jing Guo, Yan Guo () and Tie-Lin Yang ()
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Shi Yao: Xi’an Jiaotong University
Meng Zhang: Xi’an Jiaotong University
Shan-Shan Dong: Xi’an Jiaotong University
Jia-Hao Wang: Xi’an Jiaotong University
Kun Zhang: Xi’an Jiaotong University
Jing Guo: Xi’an Jiaotong University
Yan Guo: Xi’an Jiaotong University
Tie-Lin Yang: Xi’an Jiaotong University

Nature Human Behaviour, 2022, vol. 6, issue 11, 1569-1576

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41562-022-01412-9

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