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

Hassan S Dashti*, Jordi Merino, Jacqueline M Lane, Yanwei Song, Caren E Smith, Toshiko Tanaka, Nicola M Mckeown, Chandler Tucker, Dianjianyi Sun, Traci M Bartz, Ruifang Li-gao, Hoirun Nisa, Sirimon Reutrakul, Rozenn N Lemaitre, Tahani M Alshehri, Renée De mutsert, Lydia Bazzano, Lu Qi, Kristen L Knutson, Bruce M PsatyDennis O Mook-kanamori, Vesna Boraska Perica, Marian L Neuhouser, Frank A J L Scheer, Martin K Rutter, Marta Garaulet, Richa Saxena

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
Pages (from-to)473-484
JournalAmerican Journal of Clinical Nutrition
Volume110
Issue number2
DOIs
Publication statusPublished - 2019

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Keywords

  • CARDIOMETABOLIC RISK-FACTORS
  • DIETARY-INTAKE
  • EATING PATTERNS
  • GENETIC-VARIANTS
  • GENOTYPE IMPUTATION
  • GWAS
  • HEALTH
  • MENDELIAN RANDOMIZATION
  • OXFORD WEBQ
  • TYPE-2 DIABETES RISK
  • UK BIOBANK
  • breakfast
  • chronobiology
  • circadian clock
  • food timing

Cite this

Dashti, H. S., Merino, J., Lane, J. M., Song, Y., Smith, C. E., Tanaka, T., Mckeown, N. M., Tucker, C., Sun, D., Bartz, T. M., Li-gao, R., Nisa, H., Reutrakul, S., Lemaitre, R. N., Alshehri, T. M., De mutsert, R., Bazzano, L., Qi, L., Knutson, K. L., ... Saxena, R. (2019). Genome-wide association study of breakfast skipping links clock regulation with food timing. American Journal of Clinical Nutrition, 110(2), 473-484. https://doi.org/10.1093/ajcn/nqz076