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

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....

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Bibliographic Details
Published in:The American journal of clinical nutrition 2019-08, Vol.110 (2), p.473-484
Main Authors: Dashti, Hassan S, Merino, Jordi, Lane, Jacqueline M, Song, Yanwei, Smith, Caren E, Tanaka, Toshiko, McKeown, Nicola M, Tucker, Chandler, Sun, Dianjianyi, Bartz, Traci M, Li-Gao, Ruifang, Nisa, Hoirun, Reutrakul, Sirimon, Lemaitre, Rozenn N, Alshehri, Tahani M, de Mutsert, Renée, Bazzano, Lydia, Qi, Lu, Knutson, Kristen L, Psaty, Bruce M, Mook-Kanamori, Dennis O, Perica, Vesna Boraska, Neuhouser, Marian L, Scheer, Frank A JL, Rutter, Martin K, Garaulet, Marta, Saxena, Richa
Format: Article
Language:English
Subjects:
Aging
Anthropometry
Biological clocks
Biological Clocks - genetics
Biological Clocks - physiology
Body mass
Body mass index
Body size
Breakfast
Caffeine
Carbohydrate metabolism
Carbohydrates
Cereals
Cerebellum
chronobiology
circadian clock
Circadian rhythms
Consortia
Correlation analysis
Cytochrome P450
Epidemiology
Feeding Behavior
Food
food timing
Gene expression
Gene Expression Regulation
Genetic diversity
Genetic variance
Genetic Variation
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genotype
Genotype & phenotype
GWAS
Humans
Links
Mental disorders
Original Research Communications
Phenotypes
Ribonucleic acid
RNA
Schizophrenia
Signs and symptoms
Smoking
Statistical methods
Time Factors
United Kingdom
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Summary: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. 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. 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). 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). 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.
ISSN:0002-9165
1938-3207
DOI:10.1093/ajcn/nqz076