Abstract

Previous studies showed that diet and gut microbiota had a correlation with sleep. However, the potential interaction effects of diet and gut microbiota on sleep are still unclear. The phenotypic data of insomnia (including 374,505 subjects) and sleep duration (including 372,805 subjects) were obtained from the UK Biobank cohort. The Single Nucleotide Polymorphisms (SNPs) associated with 114 gut microbiota, 84 dietary habits, and 4 dietary compositions were derived from the published Genome-wide Association Study (GWAS). We used Linkage Disequilibrium Score Regression (LDSC) to estimate the genetic correlation and colocalization analysis to assess whether dietary habits and insomnia/sleep duration shared a causal variant in a region of the genome. Using UK Biobank genotype data, the polygenetic risk score of gut microbiota, dietary habits, and dietary compositions were calculated for each subject. Logistic regression and linear regression models were used to assess the potential effects of diet-gut microbiota interactions on sleep phenotypes, including insomnia and sleep duration. Insomnia and sleep duration were used as dependent variables, and sex, age, the Townsend Deprivation Index scores, and smoking and drinking habits were selected as covariates in the regression analysis. All statistical analyses were conducted using R-3.5.1 software. Significant genetic correlations were discovered between insomnia/sleep duration and dietary habits. Further, we found several significant dietary compositions-gut microbiota interactions associated with sleep, such as fat × G_Collinsella_RNT (p = 1.843 × 10−2) and protein × G_Collinsella_HB (p = 7.11 × 10−3). Besides, multiple dietary habits-gut microbiota interactions were identified for sleep, such as overall beef intake × G_Desulfovibrio_RNT (p = 3.26 × 10−4), cups of coffee per day × G_Escherichia_Shigella_RNT (p = 1.14 × 10−3), and pieces of dried fruit per day × G_Bifidobacterium_RNT (p = 5.80 × 10−3). This study reported multiple diet-gut microbiota interactions associated with sleep, which may provide insights into the biological mechanisms of diet and gut microbiota affecting sleep.

Highlights

  • We discovered multiple genetic correlation signals between insomnia and 84 dietary habits with p value < 0.05 (Supplementary Table S1)

  • For each significant dietary habit associated with insomnia, we identified the specific meaningful Single Nucleotide Polymorphisms (SNPs) using the co-localization analysis, such as rs11693221 for bread type: whole meal/whole grain vs

  • For the genetic correlation of sleep duration and 84 dietary habits, we found several significant signals with p value < 0.05 and the specific SNPs were identified by colocalization analysis, such as rs62158206 for milk type: soy milk vs. never and rs6737318 for overall lamb/mutton intake (Supplementary Tables S1 and S3)

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Summary

Introduction

One of the common types of sleep disorders, is characterized by difficulty initiating or maintaining sleep, or non-restorative sleep, which is a symptom of dissatisfaction with the quality or duration of sleep [1,2]. Insomnia may be caused by many factors, such as stress, medical conditions, the use of certain drugs, poor sleep habits, eating too much in the evening, or the change of schedule due to work or travel [1]. Insomnia affects approximately 20% of adolescent and 35% adults [3–5]. It can cause fatigue, concentration or memory impairment, and motivation or energy reduction [1]. Due to its high prevalence and its subsequent impairments, insomnia is an important public health problem, and it increases the risks of anxiety disorders, major depression, cardiovascular disease, and coronary heart disease [8–10]

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