Nutritional profile of the diet according to circadian clock genes in the European Prospective Investigation into Cancer and Nutrition (EPIC) chronodiet study

Abstract

Background & aims: Circadian rhythms seem to impact both dietary intake and metabolism, depending on the individual's chronotype. We aimed to explore whether the nutritional composition of meals throughout the day is influenced by genetics linked to the circadian clock and chronotype within the European Prospective Investigation into Cancer and Nutrition (EPIC) chronodiet study. Methods: The study population comprised 3,183 subjects with information on diet and twelve genetic variants of six genes (PER1, PER2, PER3, CRY1, NR1D1, CLOCK). The associations between the variants with chrononutrition variables (macronutrients and serving sizes of each meal) were evaluated using linear regression, considering an additive genetic model, and adjusting for sex, age and center, among others. The beta coefficients, 95 % confidence intervals (CI), and p-values corrected for multiple comparisons were estimated. A genetic risk score (GRS) that was associated to the evening/late chronotype as well as overweight/obesity in a previous study, the chronotype-GRS, was tested for its association with chrononutrition variables. Results: The nutritional profile of the diet differed according to the individual's chronotype, with evening/late chronotypes exhibiting an unbalanced intake during breakfast and dinner compared to the intermediate and early chronotypes (e.g., percentage of fats consumed at breakfast relative to the total fat intake: 13 % and 9 %, respectively). However, significant differences were not encountered by the chronotype-GRS. In multivariate analyses, individual associations between the genetic variants and the nutrients revealed some nominal associations (e.g., rs1801260 and rs2070062 with carbohydrates at breakfast: beta = -0.06 to 0.08). Higher scorings of the chronotype-GRS were inversely associated with the intake of proteins and carbohydrates (beta = -0.46 and -0.41; nominal p-value<0.006; corrected = 0.25) during breakfast. Also, there was an inverse association between the chronotype-GRS and the breakfast's portion size (beta = -0.3; nominal p-value = 0.03; corrected = 0.1). Conclusions: Genetic susceptibility to an evening-like chronotype prone to overweight/obesity seems to be associated with a smaller serving size during breakfast, with lower protein and carbohydrate content. (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).