GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person

Nat Commun. 2016 Feb 2;7:10448. doi: 10.1038/ncomms10448.

Abstract

Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10(-18); rs9479402 near VIP, P=3.9 × 10(-11); rs55694368 near PER2, P=2.6 × 10(-9); rs35833281 near HCRTR2, P=3.7 × 10(-9); rs11545787 near RASD1, P=1.4 × 10(-8); rs11121022 near PER3, P=2.0 × 10(-8); rs9565309 near FBXL3, P=3.5 × 10(-8). Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Body Mass Index
  • Circadian Rhythm / genetics*
  • Depression / epidemiology*
  • F-Box Proteins / genetics
  • Female
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Middle Aged
  • Orexin Receptors / genetics
  • Period Circadian Proteins / genetics
  • Polymorphism, Single Nucleotide
  • RGS Proteins / genetics
  • Sleep Apnea Syndromes / epidemiology*
  • Sleep Initiation and Maintenance Disorders / epidemiology*
  • Vasoactive Intestinal Peptide / genetics
  • ras Proteins / genetics

Substances

  • F-Box Proteins
  • FBXL3 protein, human
  • HCRTR2 protein, human
  • Orexin Receptors
  • PER2 protein, human
  • PER3 protein, human
  • Period Circadian Proteins
  • RASD1 protein, human
  • RGS Proteins
  • RGS16 protein
  • Vasoactive Intestinal Peptide
  • ras Proteins