Causal Effect of Relative Carbohydrate Intake on Hypertension through Psychological Well-Being and Adiposity: A Mendelian Randomization Study

Author:

Ye Chaojie12,Kong Lijie12ORCID,Wang Yiying12,Dou Chun12,Xu Min12,Zheng Jie12,Zheng Ruizhi12,Xu Yu12,Li Mian12,Zhao Zhiyun12,Lu Jieli12,Chen Yuhong12,Wang Weiqing12,Bi Yufang12,Wang Tiange12ORCID,Ning Guang12

Affiliation:

1. Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

2. Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Abstract

Observations of the association between carbohydrate intake and hypertension are inconsistent, with mediating pathways unclear. We aimed to investigate the causal effect of relative carbohydrate intake on hypertension and the mediating roles of psychological well-being and adiposity. Using summary-level statistics of genome-wide association studies of European ancestry, we conducted univariable and multivariable Mendelian randomization (MR) to estimate the bidirectional causal association between relative carbohydrate intake (total energy-adjusted, mean: 42–51%) and hypertension (FinnGen: 42,857 cases/162,837 controls; UK Biobank: 77,723 cases/330,366 controls) and two-step MR to assess the mediating effects of psychological well-being indicators and adiposity traits on the association. MR estimates of hypertension from FinnGen and UK Biobank were meta-analyzed using the fixed-effect model given no heterogeneity. Meta-analyses of multivariable MR estimates from FinnGen and UK Biobank indicated that each one-SD higher relative carbohydrate intake was associated with 71% (odds ratio: 0.29; 95% confidence interval: 0.11–0.79) lower risk of hypertension, independently of other dietary macronutrients. Hypertension showed no reverse effect on carbohydrate intake. Five psychological well-being indicators and four adiposity traits causally mediated the association between relative carbohydrate intake and hypertension, including body mass index (mediation proportion: 51.37%), waist circumference (40.54%), waist-to-hip ratio (35.00%), hip circumference (24.77%), major depressive disorder (23.37%), positive affect (17.08%), depressive symptoms (16.52%), life satisfaction (16.05%), and neuroticism (11.22%). Higher relative carbohydrate intake was causally associated with lower hypertension risk, substantially mediated by better psychological well-being and less adiposity. Our findings inform causal targets and pathways for the prevention and intervention of hypertension.

Funder

National Natural Science Foundation of China

Shanghai Jiao Tong University School of Medicine

Innovative Research Team of High-level Local Universities in Shanghai

Publisher

MDPI AG

Subject

Food Science,Nutrition and Dietetics

Reference42 articles.

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