Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms.
Level 3 - non-randomized controlled study
Non-randomized observational cohort genetic association (GWAS) and Mendelian randomization study (graded by design analogy).
PubMed 30696823 · doi:10.1038/s41467-018-08259-7
What was done
Genome-wide association analyses were performed on 697,828 participants from the UK Biobank and 23andMe to identify genetic loci associated with self-reported morning chronotype. Findings were evaluated against objective sleep timing in a subset of 85,760 individuals with activity-monitor data. Biological pathways and tissue expression enrichments were analyzed, and Mendelian randomization was applied to assess causal relationships with mental health, body mass index (BMI), and type 2 diabetes.
What was found
The study increased the number of identified morningness loci from 24 to 351. Individuals in the top 5% of morningness genetic risk had a mean sleep timing 25 minutes earlier than those in the bottom 5%. Loci were enriched for circadian regulation, cAMP, glutamate, and insulin signaling, with expression in the retina, hindbrain, hypothalamus, and pituitary. Mendelian randomization showed a causal association between morningness and better mental health, but found no effect on BMI or type 2 diabetes risk (specific effect estimates were not reported in the abstract).
Why it matters
This work expands the known genetic architecture of human circadian preference from dozens to hundreds of loci. It links genetic variation directly to objective sleep timing and provides genetic evidence connecting morning chronotype to improved mental health outcomes.
Limits
The abstract does not provide specific effect sizes, odds ratios, or confidence intervals for the Mendelian randomization outcomes. Findings are based on UK Biobank and 23andMe cohorts, which may lack ancestral diversity, and Mendelian randomization results remain subject to potential unmeasured pleiotropy.
Cited by
- contradicts Chronotypes (early bird vs. night owl) are genetically determined by a single nucleotide polymorphism in the PER3 genomic region.