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

Chaojie Ye; Lijie Kong; Yiying Wang; Chun Dou; Min Xu; Jie Zheng; Ruizhi Zheng; Yu Xu; Mian Li; Zhiyun Zhao; Jieli Lu; Yuhong Chen; Weiqing Wang; Yufang Bi; Tiange Wang; Guang Ning

doi:10.3390/nu15224817

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

Nutrients. 2023 Nov 17;15(22):4817. doi: 10.3390/nu15224817.

Authors

Chaojie Ye^{1

2}, Lijie Kong^{1

2}, Yiying Wang^{1

2}, Chun Dou^{1

2}, Min Xu^{1

2}, Jie Zheng^{1

2}, Ruizhi Zheng^{1

2}, Yu Xu^{1

2}, Mian Li^{1

2}, Zhiyun Zhao^{1

2}, Jieli Lu^{1

2}, Yuhong Chen^{1

2}, Weiqing Wang^{1

2}, Yufang Bi^{1

2}, Tiange Wang^{1

2}, Guang Ning^{1

2}

Affiliations

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.

Keywords: Mendelian randomization; adiposity; hypertension; mediation; psychological well-being; relative carbohydrate intake.

Publication types

Meta-Analysis

MeSH terms

Adiposity
Carbohydrates
Depressive Disorder, Major*
Genome-Wide Association Study
Humans
Hypertension* / complications
Hypertension* / epidemiology
Hypertension* / genetics
Mendelian Randomization Analysis
Obesity / complications
Polymorphism, Single Nucleotide
Psychological Well-Being

Substances

Carbohydrates

Abstract

Publication types

MeSH terms

Substances

Grants and funding