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Genome-wide association study of breakfast skipping links clock regulation with food timing.

ABSTRACT: BACKGROUND:Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits. OBJECTIVES:The aim of this study was to elucidate breakfast skipping genetic variants through a proxy-phenotype genome-wide association study (GWAS) for breakfast cereal skipping, a commonly assessed correlated trait. METHODS:We leveraged the statistical power of the UK Biobank (n = 193,860) to identify genetic variants related to breakfast cereal skipping as a proxy-phenotype for breakfast skipping and applied several in silico approaches to investigate mechanistic functions and links to traits/diseases. Next, we attempted validation of our approach in smaller breakfast skipping GWAS from the TwinUK (n = 2,006) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (n = 11,963). RESULTS:In the UK Biobank, we identified 6 independent GWAS variants, including those implicated for caffeine (ARID3B/CYP1A1), carbohydrate metabolism (FGF21), schizophrenia (ZNF804A), and encoding enzymes important for N6-methyladenosine RNA transmethylation (METTL4, YWHAB, and YTHDF3), which regulates the pace of the circadian clock. Expression of identified genes was enriched in the cerebellum. Genome-wide correlation analyses indicated positive correlations with anthropometric traits. Through Mendelian randomization (MR), we observed causal links between genetically determined breakfast skipping and higher body mass index, more depressive symptoms, and smoking. In bidirectional MR, we demonstrated a causal link between being an evening person and skipping breakfast, but not vice versa. We observed association of our signals in an independent breakfast skipping GWAS in another British cohort (P = 0.032), TwinUK, but not in a meta-analysis of non-British cohorts from the CHARGE consortium (P = 0.095). CONCLUSIONS:Our proxy-phenotype GWAS identified 6 genetic variants for breakfast skipping, linking clock regulation with food timing and suggesting a possible beneficial role of regular breakfast intake as part of a healthy lifestyle.

SUBMITTER: Dashti HS

PROVIDER: S-EPMC6669061 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Genome-wide association study of breakfast skipping links clock regulation with food timing.

Dashti Hassan S HS Merino Jordi J Lane Jacqueline M JM Song Yanwei Y Smith Caren E CE Tanaka Toshiko T McKeown Nicola M NM Tucker Chandler C Sun Dianjianyi D Bartz Traci M TM Li-Gao Ruifang R Nisa Hoirun H Reutrakul Sirimon S Lemaitre Rozenn N RN Alshehri Tahani M TM de Mutsert Renée R Bazzano Lydia L Qi Lu L Knutson Kristen L KL Psaty Bruce M BM Mook-Kanamori Dennis O DO Perica Vesna Boraska VB Neuhouser Marian L ML Scheer Frank A J L FAJL Rutter Martin K MK Garaulet Marta M Saxena Richa R

The American journal of clinical nutrition 20190801 2

<h4>Background</h4>Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits.<h4>Objectives</h4>The aim of this study was to elucidate breakfast skipping genetic variants through a proxy-phenotype genome-wide association study (GWAS) for breakfast cereal skip ...[more]

PMID: 31190057

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Project description:BackgroundBreakfast skipping is a common dietary habit practiced among adolescents and is strongly associated with obesity.ObjectiveThe objective was to examine whether a high-protein (HP) compared with a normal-protein (NP) breakfast leads to daily improvements in appetite, satiety, food motivation and reward, and evening snacking in overweight or obese breakfast-skipping girls.DesignA randomized crossover design was incorporated in which 20 girls [mean ± SEM age: 19 ± 1 y; body mass index (in kg/m(2)): 28.6 ± 0.7] consumed 350-kcal NP (13 g protein) cereal-based breakfasts, consumed 350-kcal HP egg- and beef-rich (35 g protein) breakfasts, or continued breakfast skipping (BS) for 6 d. On day 7, a 10-h testing day was completed that included appetite and satiety questionnaires, blood sampling, predinner food cue-stimulated functional magnetic resonance imaging brain scans, ad libitum dinner, and evening snacking.ResultsThe consumption of breakfast reduced daily hunger compared with BS with no differences between meals. Breakfast increased daily fullness compared with BS, with the HP breakfast eliciting greater increases than did the NP breakfast. HP, but not NP, reduced daily ghrelin and increased daily peptide YY concentrations compared with BS. Both meals reduced predinner amygdala, hippocampal, and midfrontal corticolimbic activation compared with BS. HP led to additional reductions in hippocampal and parahippocampal activation compared with NP. HP, but not NP, reduced evening snacking of high-fat foods compared with BS.ConclusionsBreakfast led to beneficial alterations in the appetitive, hormonal, and neural signals that control food intake regulation. Only the HP breakfast led to further alterations in these signals and reduced evening snacking compared with BS, although no differences in daily energy intake were observed. These data suggest that the addition of breakfast, particularly one rich in protein, might be a useful strategy to improve satiety, reduce food motivation and reward, and improve diet quality in overweight or obese teenage girls. This trial was registered at clinicaltrials.gov as NCT01192100.

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Genome-wide association study of breakfast skipping links clock regulation with food timing.

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Genome-wide association study of breakfast skipping links clock regulation with food timing.

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